Granted Patent B2

US 10,023,537 · App. 15/147,021 · Granted Jul 17, 2018

Abstract

Claims (23)

1. A method for the synthesis of a compound of Formula XXIV:

comprising the step of reacting a compound of Formula XXIII:

with an aldehyde or ketone of formula (R 101 )C(O)(R 103 ),

wherein represents a single or double bond;

semicircle represents an optionally substituted aryl, containing one, two or three rings;

A is selected from absent, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, —S—, —O—, —S(O)—, —S(O) 2 —, —S[C(R 10 )(R 11 )] u —, —S(O) [C(R 10 )(R 11 )] u —, —S(O) 2 [C(R 10 )(R 11 )] u —,—O[C(R 10 )(R 11 )] u —, —N(R 10 )—, —N(R 10 )—[C(R 10 )(R 11 )] u —, —[C(R 10 )(R 11 )] u ;

wherein each u is independently 1, 2, 3, 4, 5, 6 or 7;

wherein each R 10 and R 11 is independently absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl;

Cy 1 is an optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocyclyl or optionally substituted aryl;

B is a direct bond, a straight chain C 1 -C 10 alkyl, C 1 -C 10 alkenyl, C 1-C 10 alkynyl, C 1 -C 10 alkoxy, alkoxyC 1 -C 10 alkoxy, C 1 -C 10 alkylamino, alkoxyC 1 -C 10 alkylamino, C 1 -C 10 alkylcarbonylamino, C 1 -C 10 alkylaminocarbonyl, aryloxyC 1 -C 10 alkoxy, aryloxyC 1 -C 10 alkylamino, aryloxyC 1 -C 10 alkylamino carbonyl, C 1 -C 10 -alkylaminoalkylaminocarbonyl, C 1 -C 10 alkyl(N-alkyl)aminoalkyl-aminocarbonyl, alkylaminoalkylamino, alkylcarbonylaminoalkylamino, alkyl(N-alkyl)aminoalkylamino, (N-alkyl)alkylcarbonylaminoalkylamino, alkylaminoalkyl, alkylaminoalkylaminoalkyl, alkylpiperazinoalkyl, piperazinoalkyl, alkylpiperazino, alkenylaryloxyC 1-C 10 alkoxy, alkenylarylaminoC 1 -C 10 alkoxy, alkenylaryllalkylaminoC 1 -C 10 alkoxy, alkenylaryloxyC 1 -C 10 alkylamino, alkenylaryloxyC 1 -C 10 alkylaminocarbonyl, piperazinoalkylaryl, heteroarylC 1 -C 10 alkyl, heteroarylC 2 -C 10 alkenyl, heteroarylC 2 -C 10 alkynyl, heteroarylC 1 -C 10 alkylamino, heteroarylC 1 -C 10 alkoxy, heteroaryloxyC 1 -C 10 alkyl, heteroaryloxyC 2 -C 10 alkenyl, heteroaryloxyC 2 -C 10 alkynyl, heteroaryloxyC 1 -C 10 alkylamino or heteroaryloxyC 1 -C 10 alkoxy;

D is selected from absent, —O—, —NR 10 , —C(R 10 )(R 11 )— and —S—, —S(O)—, —S(O) 2 —, —C(O)—;

G 1 is present or absent, and each G 1 and G 2 is independently selected from —S—, —O—, —S(O)—, —S(O) 2 —, —SC(R 10 )(R 11 )—, —S(O) C(R 10 )(R 11 )—, —S(O) 2 C(R 10 )(R 11 )—, —OC(R 10 )(R 11 )—, —N(R 10 )—, —C(R 10 )═C(R 11 )—, —N(R 10 )—C(R 10 )(R 11 )—, or —[C(R 10 )(R 11 )] t —;

wherein t is 1, 2 or 3;

Each R 1 , R 3 and R 4 is independently selected from absent, hydrogen, halogen, —OR 10 ,—SR 10 , —N(R 10 )(R 11 ), —S(O)R 10 , —S(O) 2 R 10 , optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl;

alternatively, two R 3 and R 4 together form an optionally substituted ring; and

wherein R 101 and R 103 are independently selected from hydrogen, halogen, optionally substituted C 1 -C 8 alkyl, optionally substituted C 2 -C 8 alkenyl, optionally substituted C 2 -C 8 alkynyl, optionally substituted C 3 -C 8 cycloalkyl, optionally substituted C 1 -C 8 alkoxy, optionally substituted C 1 -C 8 alkylamino and optionally substituted C 1 -C 8 aryl; and

wherein m and q are independently selected from 0, 1, and 2.

2. The method according to claim 1 , wherein said aldehyde is paraformaldehyde.

3. The method according to claim 1 further comprising the step of reacting said compound of formula XXIV with an acid anhydride to form a compound formula XXVI,

wherein R 100 has the same meaning as R 102 and R 103 .

4. The method according to claim 3 , wherein said acid anhydride is selected from acetic anhydride, butyric anhydride, hexanoic anhydride, octanoic anhydride, decanoic anhydride, dodecanoic anhydride, lauric anhydride, and palmitic anhydride.

5. The method according to claim 1 , wherein the compound of Formula XXIII is reacted with an aldehyde.

6. The method according to claim 1 , wherein the compound of Formula XXIV has the formula:

Assignments (8)