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US 2009/0023925 A1Published application
N'-(2-halobenzylidene)sulfonylhydrazides as intermediates in the manufacture of arylsulfonylindazoles
AssigneeWyeth
InventorsAnita Wai-Yin Chan, Mahmut Levent, David Place, Panolil Raveendranath, Sanjay Raveendranth, Vijay Raveendranath, Girija Raveendranath, Xinxu Shi, Charles Wu
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Abstract
The present invention provides N′-(2-halobenzylidene)sulfonylhydrazides of formula I Compounds of formula I are useful for the manufacture of 1-arylsulfonylindazole 5-HT6 ligands.
Claims22
A compound of formula I
- wherein
- Hal is Cl, Br or I;
- R2 is an optionally substituted aryl or optionally substituted heteroaryl group;
- R3 and R4 are each independently H, NR5R6, OR7, or an optionally substituted alkyl group;
- R5 and R6 are each independently H or an optionally substituted alkyl group or R5 and R6 may be taken together with the atom to which they are attached to form an optionally substituted 5- to 7-membered ring optionally containing an additional heteroatom selected from NR8, O or S;
- R7 is H or an optionally substituted alkyl group;
- R8 is H, COR9, CO2R9, Si(R10)3 or an optionally substituted alkyl group;
- and
- R9 and R10 are each independently an optionally substituted alkyl group;
- or
- the E and Z isomers thereof.
8 more elements
A process for the manufacture of a compound of formula I
- wherein
- Hal is Cl, Br or I;
- R2 is an optionally substituted aryl or optionally substituted heteroaryl group;
- R3 and R4 are each independently H, NR5R6, OR7, or an optionally substituted alkyl group;
- R5 and R6 are each independently H or an optionally substituted alkyl group or R5 and R6 may be taken together with the atom to which they are attached to form an optionally substituted 5- to 7-membered ring optionally containing an additional heteroatom selected from NR8, O or S;
- R7 is H or an optionally substituted alkyl group;
- R8 is H, COR9, CO2R9, Si(R10)3 or an optionally substituted alkyl group;
- and
- R9 and R10 are each independently an optionally substituted alkyl group;
- which process comprises reacting a compound of formula II
- wherein Hal, R3 and R4 are as described hereinabove;
- with a sulfonylhydrazide compound of formula III
- H2NNHSO2R2 (III)
- wherein R2 is as described hereinabove;
- at a temperature of about 35° C. to 120° C., optionally in the presence of a solvent to form a compound of formula I.
12 more elements
A process for the manufacture of a compound of formula IV
- wherein
- R2 is an aryl or heteroaryl group each group optionally substituted;
- R3 and R4 are each independently H, NR5R6, OR7, or an optionally substituted alkyl group;
- R5 and R6 are each independently H or an optionally substituted alkyl group or R5 and R6 may be taken together with the atom to which they are attached to form an optionally substituted 5- to 7-membered ring optionally containing an additional heteroatom selected from NR8, O or S;
- R7 is H or an optionally substituted alkyl group;
- R8 is COR9, CO2R9, Si(R10)3 or an optionally substituted alkyl group;
- and
- R9 and R10 are each independently an optionally substituted alkyl group;
- which process comprises reacting a compound of formula I
- wherein R2, R3 and R4 are as described hereinabove;
- and Hal is Cl, Br or I with a base in the presence of a copper containing catalyst in the presence of a solvent to form a compound of formula IV.
8 more elements
A process for the manufacture of a compound of formula IV
- wherein
- R2 is an aryl or heteroaryl group each group optionally substituted;
- R3 and R4 are each independently H, NR5R6, OR7, or an optionally substituted alkyl group;
- R5 and R6 are each independently H or an optionally substituted alkyl group or R5 and R6 may be taken together with the atom to which they are attached to form an optionally substituted 5- to 7-membered ring optionally containing an additional heteroatom selected from NR8, O or S;
- R7 is H or an optionally substituted alkyl group;
- R8 is COR9, CO2R9, Si(R10)3 or an optionally substituted alkyl group;
- and
- R9 and R10 are each independently an optionally substituted alkyl group;
- which process comprises reacting compound of formula II
- wherein Hal represents Cl, Br or I and R3 and R4 are as described hereinabove;
- with a sulfonylhydrazide compound of formula III
- H2NNHSO2R2 (III)
- wherein R2 is as described hereinabove;
- at a temperature of about 35° C. to 120° C., optionally in the presence of a first solvent to give a compound of formula I
- wherein Hal represents Cl, Br or I and R2, R3 and R4 are as described hereinabove;
- and reacting said formula I compound with a base in the presence of a copper containing catalyst in the presence of a second solvent.
13 more elements
A process for the manufacture of a compound of formula IVa or a pharmaceutically acceptable salt thereof
- wherein
- R2 is an aryl or heteroaryl group each group optionally substituted;
- R3 and R4 are each independently NR5R6 provided that at least one of R3 and R4 is NR5R6;
- R5 and R6 are taken together with the atom to which they are attached to form an optionally substituted 5- to 7-membered ring optionally containing NR8;
- and
- R8 is H;
- which process comprises contacting a compound of formula IVb
- wherein
- R2 is an aryl or heteroaryl group each group optionally substituted;
- R3 and R4 are each independently NR5R6 provided that at least one of R3 and R4 is NR5R6;
- R5 and R6 are taken together with the atom to which they are attached to form an optionally substituted 5- to 7-membered ring optionally containing NR8;
- R8 is COR9, CO2R9, or Si(R10)3;
- and
- R9 and R10 are each independently an optionally substituted alkyl group,
- with a deprotecting agent, thereby removing R8 of formula IVb to form the compound of formula IVa;
- and optionally reacting with an acid to form the pharmaceutically acceptable salt of the compound of formula IVa.
13 more elements
Dependencies are inferred from the claim text.