IP Library › Patent Application 13605961
Patent Application
App. No. 13/605,961

Compounds for Use in Treating Neurodegenerative Disorders, Synthesis Thereof, and Intermediates Thereto

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Patent No.
US None
App. No.
13/605,961
Abstract

The present invention provides methods of making a compound of formula II: or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , and L are as defined and described herein.

Claims (135)

1 . A method for preparing a compound of formula II:

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is independently R, S(O)R, SO 2 R, C(O)R, CO 2 R, or C(O)N(R) 2 , an optionally substituted aliphatic group, a suitably protected amino group, an optionally substituted 3-8 membered saturated, partially unsaturated, or aryl monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, an optionally substituted 8-10 membered saturated, partially unsaturated, or aryl bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

each R is independently deuterium, hydrogen, an optionally substituted C 1-6 aliphatic group, an optionally substituted C 1-6 heteroaliphatic group, or an optionally substituted 3-8 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein:

two R on the same nitrogen atom are optionally taken together with said nitrogen atom to form an optionally substituted 3-8 membered, saturated, partially unsaturated, or aryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

L is a valence bond or an optionally substituted C 1-10 alkylene chain wherein one, two, or three methylene units of L are optionally and independently replaced by —O—, —N(R)—, —S—, —C(O)—, —OC(O)—, —C(O)O—, —OC(O)O—, —S(O)—, or —S(O) 2 —, —OSO 2 O—, —NRC(O)—, —C(O)NR—, —N(R)C(O)O—, —OC(O)NR—, —N(R)C(O)NR—, or -Cy-, wherein:

each -Cy- is independently a bivalent optionally substituted saturated, partially unsaturated, or aromatic monocyclic or bicyclic ring selected from a 6-10 membered arylene, a 5-10 membered heteroarylene having 1-4 heteroatoms independently selected from oxygen, nitrogen, or sulfur, a 3-8 membered carbocyclylene, or a 3-10 membered heterocyclylene having 1-4 heteroatoms independently selected from oxygen, nitrogen, or sulfur; and

R 2 is halogen or R.

comprising the steps of:

(a) extracting from biomass a compound of formula A:

(b) treating said compound of formula A with a suitable acid to form a compound of formula B:

(c) treating said compound of formula B with a suitable oxidant to provide a compound of formula C:

(d) treating said compound of formula C with a suitable amine, or salt thereof, in the presence of a base to provide a compound of formula D:

wherein:

L is a valence bond or an optionally substituted C 1-10 alkylene chain wherein one, two, or three methylene units of L are optionally and independently replaced by —O—, —N(R)—, —S—, —C(O)—, —OC(O)—, —C(O)O—, —OC(O)O—, —S(O)—, or —S(O) 2 —, —OSO 2 O—, —NRC(O)—, —C(O)NR—, —N(R)C(O)O—, —OC(O)NR—, —N(R)C(O)NR—, or -Cy-, wherein:

each -Cy- is independently a bivalent optionally substituted saturated, partially unsaturated, or aromatic monocyclic or bicyclic ring selected from a 6-10 membered arylene, a 5-10 membered heteroarylene having 1-4 heteroatoms independently selected from oxygen, nitrogen, or sulfur, a 3-8 membered carbocyclylene, or a 3-10 membered heterocyclylene having 1-4 heteroatoms independently selected from oxygen, nitrogen, or sulfur; and

each R is independently deuterium, hydrogen, an optionally substituted C 1-6 aliphatic group, an optionally substituted C 1-6 heteroaliphatic group, or an optionally substituted 3-8 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein:

two R on the same nitrogen atom are optionally taken together with said nitrogen atom to form an optionally substituted 3-8 membered, saturated, partially unsaturated, or aryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; and

PG 1 is a suitable amino protecting group;

(e) reducing the carbonyl component of said compound of formula D to form a compound of formula E:

wherein:

L is a valence bond or an optionally substituted C 1-10 alkylene chain wherein one, two, or three methylene units of L are optionally and independently replaced by —O—, —N(R)—, —S—, —C(O)—, —OC(O)—, —C(O)O—, —OC(O)O—, —S(O)—, or —S(O) 2 —, —OSO 2 O—, —NRC(O)—, —C(O)NR—, —N(R)C(O)O—, —OC(O)NR—, —N(R)C(O)NR—, or -Cy-, wherein:

each -Cy- is independently a bivalent optionally substituted saturated, partially unsaturated, or aromatic monocyclic or bicyclic ring selected from a 6-10 membered arylene, a 5-10 membered heteroarylene having 1-4 heteroatoms independently selected from oxygen, nitrogen, or sulfur, a 3-8 membered carbocyclylene, or a 3-10 membered heterocyclylene having 1-4 heteroatoms independently selected from oxygen, nitrogen, or sulfur; and

each R is independently deuterium, hydrogen, an optionally substituted C 1-6 aliphatic group, an optionally substituted C 1-6 heteroaliphatic group, or an optionally substituted 3-8 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein:

two R on the same nitrogen atom are optionally taken together with said nitrogen atom to form an optionally substituted 3-8 membered, saturated, partially unsaturated, or aryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; and

PG 1 is a suitable amino protecting group;

(f) protecting said compound of formula E to form a compound of formula F:

wherein:

L is a valence bond or an optionally substituted C 1-10 alkylene chain wherein one, two, or three methylene units of L are optionally and independently replaced by —O—, —N(R)—, —S—, —C(O)—, —OC(O)—, —C(O)O—, —OC(O)O—, —S(O)—, or —S(O) 2 —, —OSO 2 O—, —NRC(O)—, —C(O)NR—, —N(R)C(O)O—, —OC(O)NR—, —N(R)C(O)NR—, or -Cy-, wherein:

each -Cy- is independently a bivalent optionally substituted saturated, partially unsaturated, or aromatic monocyclic or bicyclic ring selected from a 6-10 membered arylene, a 5-10 membered heteroarylene having 1-4 heteroatoms independently selected from oxygen, nitrogen, or sulfur, a 3-8 membered carbocyclylene, or a 3-10 membered heterocyclylene having 1-4 heteroatoms independently selected from oxygen, nitrogen, or sulfur; and

each R is independently deuterium, hydrogen, an optionally substituted C 1-6 aliphatic group, an optionally substituted C 1-6 heteroaliphatic group, or an optionally substituted 3-8 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein:

two R on the same nitrogen atom are optionally taken together with said nitrogen atom to form an optionally substituted 3-8 membered, saturated, partially unsaturated, or aryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; and

PG 1 is a suitable amino protecting group; and

PG 2 is a suitable oxygen protecting group;

(g) deacetylating said compound of formula F to form a compound of formula G:

wherein:

L is a valence bond or an optionally substituted C 1-10 alkylene chain wherein one, two, or three methylene units of L are optionally and independently replaced by —O—, —N(R)—, —S—, —C(O)—, —OC(O)—, —C(O)O—, —OC(O)O—, —S(O)—, or —S(O) 2 —, —OSO 2 O—, —NRC(O)—, —C(O)NR—, —N(R)C(O)O—, —OC(O)NR—, —N(R)C(O)NR—, or -Cy-, wherein:

each -Cy- is independently a bivalent optionally substituted saturated, partially unsaturated, or aromatic monocyclic or bicyclic ring selected from a 6-10 membered arylene, a 5-10 membered heteroarylene having 1-4 heteroatoms independently selected from oxygen, nitrogen, or sulfur, a 3-8 membered carbocyclylene, or a 3-10 membered heterocyclylene having 1-4 heteroatoms independently selected from oxygen, nitrogen, or sulfur; and

each R is independently deuterium, hydrogen, an optionally substituted C 1-6 aliphatic group, an optionally substituted C 1-6 heteroaliphatic group, or an optionally substituted 3-8 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein:

two R on the same nitrogen atom are optionally taken together with said nitrogen atom to form an optionally substituted 3-8 membered, saturated, partially unsaturated, or aryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; and

PG 1 is a suitable amino protecting group; and

PG 2 is a suitable oxygen protecting group;

(h) reacting said compound of formula G to form a compound of formula H:

wherein:

R 1 is independently R, S(O)R, SO 2 R, C(O)R, CO 2 R, or C(O)N(R) 2 , an optionally substituted aliphatic group, a suitably protected amino group, an optionally substituted 3-8 membered saturated, partially unsaturated, or aryl monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, an optionally substituted 8-10 membered saturated, partially unsaturated, or aryl bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

L is a valence bond or an optionally substituted C 1-10 alkylene chain wherein one, two, or three methylene units of L are optionally and independently replaced by —O—, —N(R)—, —S—, —C(O)—, —OC(O)—, —C(O)O—, —OC(O)O—, —S(O)—, or —S(O) 2 —, —OSO 2 O—, —NRC(O)—, —C(O)NR—, —N(R)C(O)O—, —OC(O)NR—, —N(R)C(O)NR—, or -Cy-, wherein:

each -Cy- is independently a bivalent optionally substituted saturated, partially unsaturated, or aromatic monocyclic or bicyclic ring selected from a 6-10 membered arylene, a 5-10 membered heteroarylene having 1-4 heteroatoms independently selected from oxygen, nitrogen, or sulfur, a 3-8 membered carbocyclylene, or a 3-10 membered heterocyclylene having 1-4 heteroatoms independently selected from oxygen, nitrogen, or sulfur; and

each R is independently deuterium, hydrogen, an optionally substituted C 1-6 aliphatic group, an optionally substituted C 1-6 heteroaliphatic group, or an optionally substituted 3-8 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein:

two R on the same nitrogen atom are optionally taken together with said nitrogen atom to form an optionally substituted 3-8 membered, saturated, partially unsaturated, or aryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; and

PG 1 is a suitable amino protecting group; and

PG 2 is a suitable oxygen protecting group;

(i) deprotecting said compound of formula H to form a compound of formula J:

wherein:

R 1 is independently R, S(O)R, SO 2 R, C(O)R, CO 2 R, or C(O)N(R) 2 , an optionally substituted aliphatic group, a suitably protected amino group, an optionally substituted 3-8 membered saturated, partially unsaturated, or aryl monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, an optionally substituted 8-10 membered saturated, partially unsaturated, or aryl bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

L is a valence bond or an optionally substituted C 1-10 alkylene chain wherein one, two, or three methylene units of L are optionally and independently replaced by —O—, —N(R)—, —S—, —C(O)—, —OC(O)—, —C(O)O—, —OC(O)O—, —S(O)—, or —S(O) 2 —, —OSO 2 O—, —NRC(O)—, —C(O)NR—, —N(R)C(O)O—, —OC(O)NR—, —N(R)C(O)NR—, or -Cy-, wherein:

each -Cy- is independently a bivalent optionally substituted saturated, partially unsaturated, or aromatic monocyclic or bicyclic ring selected from a 6-10 membered arylene, a 5-10 membered heteroarylene having 1-4 heteroatoms independently selected from oxygen, nitrogen, or sulfur, a 3-8 membered carbocyclylene, or a 3-10 membered heterocyclylene having 1-4 heteroatoms independently selected from oxygen, nitrogen, or sulfur; and

each R is independently deuterium, hydrogen, an optionally substituted C 1-6 aliphatic group, an optionally substituted C 1-6 heteroaliphatic group, or an optionally substituted 3-8 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein:

two R on the same nitrogen atom are optionally taken together with said nitrogen atom to form an optionally substituted 3-8 membered, saturated, partially unsaturated, or aryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

(j) reacting said compound of formula J under suitable conditions to form a compound of formula II.

2 . The method of claim 1 , wherein L is a valence bond.

3 . The method of claim 1 , wherein L is an optionally substituted C 1-10 alkylene chain wherein one, two, or three methylene units of L are optionally and independently replaced by —O—, —N(R)—, —S—, —C(O)—, —OC(O)—, —C(O)O—, —OC(O)O—, —S(O)—, or —S(O) 2 —, —OSO 2 O—, —NRC(O)—, —C(O)NR—, —N(R)C(O)O—, —OC(O)NR—, —N(R)C(O)NR—, or -Cy-.

4 . The method of claim 3 , wherein each -Cy- is independently a bivalent optionally substituted saturated, partially unsaturated, or aromatic monocyclic or bicyclic ring selected from a 5-10 membered heteroarylene having 1-4 heteroatoms independently selected from oxygen, nitrogen, or sulfur, or a 3-10 membered heterocyclylene having 1-4 heteroatoms independently selected from oxygen, nitrogen, or sulfur.

5 . The method of claim 3 , wherein L is of either of the following formulae:

6 . The method of claim 1 , wherein PG 1 is t-butyloxycarbonyl (BOC), ethyloxycarbonyl, methyloxycarbonyl, trichloroethyloxycarbonyl, allyloxycarbonyl (Alloc), benzyloxocarbonyl (CBZ), allyl, phthalimide, benzyl (Bn), fluorenylmethylcarbonyl (Fmoc), formyl, acetyl, chloroacetyl, dichloroacetyl, trichloroacetyl, phenylacetyl, trifluoroacetyl, or benzoyl.

7 . The method of claim 1 , wherein R 2 is R.

8 . The method of claim 7 , wherein R 2 is an optionally substituted C 1-6 heteroaliphatic group or optionally substituted C —-6 aliphatic group.

9 . The method of claim 8 , wherein R 2 is

10 . The method of claim 1 , wherein step (h) is an alkylation reaction.

11 . The method of claim 1 , wherein the deprotection of step (i) occurs in a single step.

12 . The method of claim 1 , wherein step (j) is an N-alkylation reaction.

13 . A method for preparing a compound of formula II:

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is independently R, S(O)R, SO 2 R, C(O)R, CO 2 R, or C(O)N(R) 2 , an optionally substituted aliphatic group, a suitably protected amino group, an optionally substituted 3-8 membered saturated, partially unsaturated, or aryl monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, an optionally substituted 8-10 membered saturated, partially unsaturated, or aryl bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

each R is independently deuterium, hydrogen, an optionally substituted C 1-6 aliphatic group, an optionally substituted C 1-6 heteroaliphatic group, or an optionally substituted 3-8 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein:

two R on the same nitrogen atom are optionally taken together with said nitrogen atom to form an optionally substituted 3-8 membered, saturated, partially unsaturated, or aryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

L is a valence bond or an optionally substituted C 1-10 alkylene chain wherein one, two, or three methylene units of L are optionally and independently replaced by —O—, —N(R)—, —S—, —C(O)—, —OC(O)—, —C(O)O—, —OC(O)O—, —S(O)—, or —S(O) 2 —, —OSO 2 O—, —NRC(O)—, —C(O)NR—, —N(R)C(O)O—, —OC(O)NR—, —N(R)C(O)NR—, or -Cy-, wherein:

each -Cy- is independently a bivalent optionally substituted saturated, partially unsaturated, or aromatic monocyclic or bicyclic ring selected from a 6-10 membered arylene, a 5-10 membered heteroarylene having 1-4 heteroatoms independently selected from oxygen, nitrogen, or sulfur, a 3-8 membered carbocyclylene, or a 3-10 membered heterocyclylene having 1-4 heteroatoms independently selected from oxygen, nitrogen, or sulfur; and

R 2 is halogen or R.

comprising the steps of:

(a) extracting from biomass a compound of formula A:

(b) treating said compound of formula A with a suitable acid to form a compound of formula B:

(c) treating said compound of formula B with a suitable oxidant to provide a compound of formula C:

(d) treating said compound of formula C with a suitable amine, or salt thereof, in the presence of a base to provide a compound of formula D-1:

wherein:

PG 1 is a suitable amino protecting group;

(e) reducing the carbonyl component of said compound of formula D-1 to form a compound of formula E-1:

wherein:

PG 1 is a suitable amino protecting group;

(f) protecting said compound of formula E-1 to form a compound of formula F-1:

wherein:

PG 1 is a suitable amino protecting group; and

PG 2 is a suitable oxygen protecting group;

(g) deacetylating said compound of formula F-1 to form a compound of formula G-1:

wherein:

PG 1 is a suitable amino protecting group; and

PG 2 is a suitable oxygen protecting group;

(h) reacting said compound of formula G-1 to form a compound of formula H-1:

wherein:

R 1 is independently R, S(O)R, SO 2 R, C(O)R, CO 2 R, or C(O)N(R) 2 , an optionally substituted aliphatic group, a suitably protected amino group, an optionally substituted 3-8 membered saturated, partially unsaturated, or aryl monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, an optionally substituted 8-10 membered saturated, partially unsaturated, or aryl bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

each R is independently deuterium, hydrogen, an optionally substituted C 1-6 aliphatic group, an optionally substituted C 1-6 heteroaliphatic group, or an optionally substituted 3-8 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein:

two R on the same nitrogen atom are optionally taken together with said nitrogen atom to form an optionally substituted 3-8 membered, saturated, partially unsaturated, or aryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; and

PG 1 is a suitable amino protecting group; and

PG 2 is a suitable oxygen protecting group;

(i) deprotecting said compound of formula H-1 to form a compound of formula I:

wherein:

R 1 is independently R, S(O)R, SO 2 R, C(O)R, CO 2 R, or C(O)N(R) 2 , an optionally substituted aliphatic group, a suitably protected amino group, an optionally substituted 3-8 membered saturated, partially unsaturated, or aryl monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, an optionally substituted 8-10 membered saturated, partially unsaturated, or aryl bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

L is a valence bond or an optionally substituted C 1-10 alkylene chain wherein one, two, or three methylene units of L are optionally and independently replaced by —O—, —N(R)—, —S—, —C(O)—, —OC(O)—, —C(O)O—, —OC(O)O—, —S(O)—, or —S(O) 2 —, —OSO 2 O—, —NRC(O)—, —C(O)NR—, —N(R)C(O)O—, —OC(O)NR—, —N(R)C(O)NR—, or -Cy-, wherein:

each -Cy- is independently a bivalent optionally substituted saturated, partially unsaturated, or aromatic monocyclic or bicyclic ring selected from a 6-10 membered arylene, a 5-10 membered heteroarylene having 1-4 heteroatoms independently selected from oxygen, nitrogen, or sulfur, a 3-8 membered carbocyclylene, or a 3-10 membered heterocyclylene having 1-4 heteroatoms independently selected from oxygen, nitrogen, or sulfur; and

each R is independently deuterium, hydrogen, an optionally substituted C 1-6 aliphatic group, an optionally substituted C 1-6 heteroaliphatic group, or an optionally substituted 3-8 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein:

two R on the same nitrogen atom are optionally taken together with said nitrogen atom to form an optionally substituted 3-8 membered, saturated, partially unsaturated, or aryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; and

(j) reacting said compound of formula I under suitable conditions to form a compound of formula II.

14 . The method of claim 13 , wherein L is a valence bond.

15 . The method of claim 13 , wherein L is an optionally substituted C 1-10 alkylene chain wherein one, two, or three methylene units of L are optionally and independently replaced by —O—, —N(R)—, —S—, —C(O)—, —OC(O)—, —C(O)O—, —OC(O)O—, —S(O)—, or —S(O) 2 —, —OSO 2 O—, —NRC(O)—, —C(O)NR—, —N(R)C(O)O—, —OC(O)NR—, —N(R)C(O)NR—, or -Cy-.

16 . The method of claim 15 , wherein each -Cy- is independently a bivalent optionally substituted saturated, partially unsaturated, or aromatic monocyclic or bicyclic ring selected from a 5-10 membered heteroarylene having 1-4 heteroatoms independently selected from oxygen, nitrogen, or sulfur, or a 3-10 membered heterocyclylene having 1-4 heteroatoms independently selected from oxygen, nitrogen, or sulfur.

17 . The method of claim 16 , wherein L is of either of the following formulae:

18 . The method of claim 13 , wherein PG 1 is t-butyloxycarbonyl (BOC), ethyloxycarbonyl, methyloxycarbonyl, trichloroethyloxycarbonyl, allyloxycarbonyl (Alloc), benzyloxocarbonyl (CBZ), allyl, phthalimide, benzyl (Bn), fluorenylmethylcarbonyl (Fmoc), formyl, acetyl, chloroacetyl, dichloroacetyl, trichloroacetyl, phenylacetyl, trifluoroacetyl, or benzoyl.

19 . The method of claim 13 , wherein the deprotection at step (i) comprises a first step of deprotecting amino protecting group PG 1 and a second step of deprotecting oxygen protecting group PG 2 .

20 . The method of claim 13 , wherein the formation of a compound of formula II at step (j) from a compound of formula I comprises steps of:

(i) reacting a compound of formula I under suitable conditions to provide a compound of formula K:

wherein:

R 1 is independently R, S(O)R, SO 2 R, C(O)R, CO 2 R, or C(O)N(R) 2 , an optionally substituted aliphatic group, a suitably protected amino group, an optionally substituted 3-8 membered saturated, partially unsaturated, or aryl monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, an optionally substituted 8-10 membered saturated, partially unsaturated, or aryl bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

L is a valence bond or an optionally substituted C 1-10 alkylene chain wherein one, two, or three methylene units of L are optionally and independently replaced by —O—, —N(R)—, —S—, —C(O)—, —OC(O)—, —C(O)O—, —OC(O)O—, —S(O)—, or —S(O) 2 —, —OSO 2 O—, —NRC(O)—, —C(O)NR—, —N(R)C(O)O—, —OC(O)NR—, —N(R)C(O)NR—, or -Cy-, wherein:

each -Cy- is independently a bivalent optionally substituted saturated, partially unsaturated, or aromatic monocyclic or bicyclic ring selected from a 6-10 membered arylene, a 5-10 membered heteroarylene having 1-4 heteroatoms independently selected from oxygen, nitrogen, or sulfur, a 3-8 membered carbocyclylene, or a 3-10 membered heterocyclylene having 1-4 heteroatoms independently selected from oxygen, nitrogen, or sulfur; and

each R is independently deuterium, hydrogen, an optionally substituted C 1-6 aliphatic group, an optionally substituted C 1-6 heteroaliphatic group, or an optionally substituted 3-8 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein:

two R on the same nitrogen atom are optionally taken together with said nitrogen atom to form an optionally substituted 3-8 membered, saturated, partially unsaturated, or aryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; and

and PG 4 is an amino protecting group;

(ii) deprotecting a compound of formula K to provide a compound of formula J:

wherein:

R 1 is independently R, S(O)R, SO 2 R, C(O)R, CO 2 R, or C(O)N(R) 2 , an optionally substituted aliphatic group, a suitably protected amino group, an optionally substituted 3-8 membered saturated, partially unsaturated, or aryl monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, an optionally substituted 8-10 membered saturated, partially unsaturated, or aryl bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

L is a valence bond or an optionally substituted C 1-10 alkylene chain wherein one, two, or three methylene units of L are optionally and independently replaced by —O—, —N(R)—, —S—, —C(O)—, —OC(O)—, —C(O)O—, —OC(O)O—, —S(O)—, or —S(O) 2 —, —OSO 2 O—, —NRC(O)—, —C(O)NR—, —N(R)C(O)O—, —OC(O)NR—, —N(R)C(O)NR—, or -Cy-, wherein:

each -Cy- is independently a bivalent optionally substituted saturated, partially unsaturated, or aromatic monocyclic or bicyclic ring selected from a 6-10 membered arylene, a 5-10 membered heteroarylene having 1-4 heteroatoms independently selected from oxygen, nitrogen, or sulfur, a 3-8 membered carbocyclylene, or a 3-10 membered heterocyclylene having 1-4 heteroatoms independently selected from oxygen, nitrogen, or sulfur; and

each R is independently deuterium, hydrogen, an optionally substituted C 1-6 aliphatic group, an optionally substituted C 1-6 heteroaliphatic group, or an optionally substituted 3-8 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein:

two R on the same nitrogen atom are optionally taken together with said nitrogen atom to form an optionally substituted 3-8 membered, saturated, partially unsaturated, or aryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; and

(iii) reacting a compound of formula J to provide a compound of formula II.

21 - 47 . (canceled)

Assignments (2)
SECURITY AGREEMENT Recorded Oct 8, 2013
From: SATORI PHARMACEUTICALS INCORPORATED
To: LIGHTHOUSE CAPITAL PARTNERS VI, L.P.
Reel/Frame 031378/0025 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 28, 2012
From: BRONK, BRIAN SCOTT; AUSTIN, WESLEY FRANCIS; CREASER, STEFFEN PHILLIP; FULLER, NATHAN OLIVER; HUBBS, JED LEE; SHEN, RUICHAO
To: SATORI PHARMACEUTICALS, INC.
Reel/Frame 029048/0701 →