IP Library Granted Patent US 10,654,803
Granted Patent B2
US 10,654,803 · App. 16/280,068 · Granted May 19, 2020

Transition metal-catalyzed protodecarboxylation of alpha-halo-acrylic acid derivatives

Inventors: Mai Thi Quynh Dang (Ingelheim am Rhein, DE); Thomas Armin Hampel (Frankfurt, DE); Sandra Koch (Wiesbaden, DE); Fredrik Lars Nordstrom (Ridgefield, CT); Jonathan Timothy Reeves (New Milford, CT); Carsten Reichel (Rheinboellen, DE); Marvin Schoerer (Oberhausen, DE); Christian Stange (Ingelheim am Rhein, DE); Ivan N. Volchkov (Sandy Hook, CT); Li Zhong (New Milford, CT); Uwe Johannes Zimmermann (Trebur, DE)
Assignee: Boehringer Ingelheim International GmbH
C07D209/48C07C231/12
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Quick Facts
Patent No.
US 10,654,803
App. No.
16/280,068
Granted
May 19, 2020
Kind
B2
Abstract

The present invention relates to a method for the synthesis of a halo olefin of formula (I) wherein Ha1, R 1 , R 2 , R 3 , R 4 , X and Y are as defined herein, or a salt thereof.

Claims (27)

1. A compound selected from the group consisting of

wherein

R ar is selected from the group consisting of C(O)NR N1 R N2 and SO 2 NR N1 R N2 , wherein R N1 and R N2 are independently selected from the group consisting of H, substituted or unsubstituted C 1-6 -alkyl and substituted or unsubstituted C 3-7 -cycloalkyl; and

R Y1 and R Y2 are independently selected from the group consisting of H, substituted or unsubstituted acetyl, substituted or unsubstituted tert-butyloxycarbonyl (Boc), substituted or unsubstituted carboxybenzyl (Cbz), substituted or unsubstituted fluorenylmethyloxycarbonyl (Fmoc), substituted or unsubstituted allyloxycarbonyl (Alloc), substituted or unsubstituted tert-butyl, substituted or unsubstituted benzyl and substituted or unsubstituted phthaloyl, provided that at least one of R Y1 and R Y2 is not H, or

R Y1 and R Y2 are linked to form, together with N to which they are attached, substituted or unsubstituted phthalimide or substituted or unsubstituted pyrrole.

2. A compound selected from the group consisting of

wherein

R ar is selected from the group consisting of C(O)NR N1 R N2 and SO 2 NR N1 R N2 , wherein R N1 and R N2 are independently selected from the group consisting of H, substituted or unsubstituted C 1-6 -alkyl and substituted or unsubstituted C 3-7 -cycloalkyl; and

R Y1 and R Y2 are independently selected from the group consisting of H, substituted or unsubstituted acetyl, substituted or unsubstituted tert-butyloxycarbonyl (Boc), substituted or unsubstituted carboxybenzyl (Cbz), substituted or unsubstituted fluorenylmethyloxycarbonyl (Fmoc), substituted or unsubstituted allyloxycarbonyl (Alloc), substituted or unsubstituted tert-butyl, substituted or unsubstituted benzyl and substituted or unsubstituted phthaloyl or

R Y1 and R Y2 are linked to form, together with N to which they are attached, substituted or unsubstituted phthalimide or substituted or unsubstituted pyrrole.

3. A compound selected from the group consisting of

wherein

R ar is selected from the group consisting of C(O)NR N1 R N2 and SO 2 NR N1 R N2 , wherein R N1 and R N2 are independently selected from the group consisting of H, substituted or unsubstituted C 1-6 -alkyl and substituted or unsubstituted C 3-7 -cycloalkyl; and

R Y1 and R Y2 are independently selected from the group consisting of H, substituted or unsubstituted acetyl, substituted or unsubstituted tert-butyloxycarbonyl (Boc), substituted or unsubstituted carboxybenzyl (Cbz), substituted or unsubstituted fluorenylmethyloxycarbonyl (Fmoc), substituted or unsubstituted allyloxycarbonyl (Alloc), substituted or unsubstituted tert-butyl, substituted or unsubstituted benzyl and substituted or unsubstituted phthaloyl or

R Y1 and R Y2 are linked to form, together with N to which they are attached,

substituted or unsubstituted phthalimide or substituted or unsubstituted pyrrole; and

R 0 is selected from the group consisting of H and C 1-6 -alkyl.

4. A compound selected from the group consisting of

wherein

R ar is selected from the group consisting of C(O)NR N1 R N2 and SO 2 NR N1 R N2 , wherein R N1 and R N2 are independently selected from the group consisting of H, substituted or unsubstituted C 1-6 -alkyl and substituted or unsubstituted C 3-7 -cycloalkyl; and

R Y1 and R Y2 are independently selected from the group consisting of H, substituted or unsubstituted acetyl, substituted or unsubstituted tert-butyloxycarbonyl (Boc), substituted or unsubstituted carboxybenzyl (Cbz), substituted or unsubstituted fluorenylmethyloxycarbonyl (Fmoc), substituted or unsubstituted allyloxycarbonyl (Alloc), substituted or unsubstituted tert-butyl, substituted or unsubstituted benzyl and substituted or unsubstituted phthaloyl or

R Y1 and R Y2 are linked to form, together with N to which they are attached, substituted or unsubstituted phthalimide or substituted or unsubstituted pyrrole.

5. The compound of claim 1 which is compound (I-j).

6. The compound of claim 2 which is compound (II-j).

7. The compound of claim 2 which is compound (II-k).

8. The compound of claim 3 which is compound (II′-k).

9. The compound of claim 4 which is compound (III-j).

Continuity (4)
Continuation 15901921 · Feb 22, 2018
Provisional Application 62512777 · May 31, 2017
Provisional Application 62465398 · Mar 1, 2017
Related Publication 20190177273A1 · Jun 13, 2019