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US 2009/0156826 A1Published application
Methods for the preparation of hydroxy-substituted aryl sulfamide compounds
AssigneeWyeth
InventorsMaria Papamichelakis, Jacqueline Francesca Lunetta, Mark Lankau, Luc Richard, Christopher Kendall, Marcelo Cesar Saraiva, Xianghui Wen, Mahmoud Mirmehrabi, Valerie Paquet, Sylvain Daigneault, Puwen Zhang
Life of this patent
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Abstract
The present invention is directed to processes for the preparation of hydroxy-substituted aryl sulfamide derivatives of the formula I or pharmaceutically acceptable salts, stereoisomers or tautomers thereof, which are monoamine reuptake inhibitors wherein the constituent variables are as defined herein.
Claims29
A compound formula IA:
- or a tautomer or salt thereof;
- wherein:
- m is an integer from 1 to 3;
- n is an integer from 0 to 4;
- R1 is, independently at each occurrence, C1-C6alkyl, C1-C6alkoxy, halo, CF3, OCF3, hydroxy, C1-C5alkylC(O)O—, nitro, —CN, C2-C6alkenyl, C2-C6alkynyl, C6-C10aryl, C4-C10heteroaryl, C1-C6alkylS(O)—, C1-C6alkylS(O)2—, C1-C6alkylS(O)2NH—, C1-C6alkylS(O)2N(C1-C6alkyl)-, C6-C10arylS(O)2NH—, C6-C10arylS(O)2N(C1-C6alkyl)- C1-C5alkylC(O)NH—, C1-C5alkylC(O)N(C1-C6alkyl)-, or C6-C10arylC(O)NH—, C6-C10arylC(O)N(C1-C6alkyl)-;
- wherein each C6-C10aryl or C4-C10heteroaryl is independently substituted with 0-3 C1-C6alkyl, C1-C6alkoxy, halo, CF3, OCF3, hydroxy, C1-C5alkylC(O)O—, nitro, —CN, C2-C6alkenyl, or C2-C6alkynyl groups;
- and each C6-C10arylS(O)2NH—, C6-C10arylS(O)2N(C1-C6alkyl)- or C6-C10arylC(O)NH—, C6-C10arylC(O)N(C1-C6alkyl)- is independently substituted with 0-3 C1-C6alkyl, C1-C6alkoxy, halo, CF3, OCF3, hydroxy, C1-C5alkylC(O)O—, nitro, —CN, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkylS(O)—, C1-C6alkylS(O)2—, C1-C6alkylS(O)2NH—, C1-C6alkylS(O)2N(C1-C6alkyl)-, C1-C5alkylC(O)NH—, or C1-C5alkylC(O)N(C1-C6alkyl)- groups;
- R2 is C6-C10aryl or C4-C10heteroaryl substituted with 0-5 C1-C6alkyl, C1-C6alkoxy, halo, CF3, OCF3, hydroxy, C1-C5alkylC(O)O—, nitro, —CN, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkylS(O)—, C1-C6alkylS(O)2—, C1-C6alkylS(O)2NH—, C1-C6alkylS(O)2N(C1-C6alkyl)-, C6-C10arylS(O)2NH—, C6-C10arylS(O)2N(C1-C6alkyl)-, C1-C5alkylC(O)NH—, C1-C5alkylC(O)N(C1-C6alkyl)-, C6-C10arylC(O)NH—, C6-C10arylC(O)N(C1-C6alkyl)-, or C6-C10aryl or C4-C10heteroaryl optionally substituted with C1-C6alkyl, C1-C6alkoxy, halo, CF3, OCF3, hydroxy, C1-C5alkylC(O)O—, nitro, —CN, C2-C6alkenyl, or C2-C6alkynyl;
- and
- represents an S-isomer, R-isomer or racemate.
7 more elements
A process comprising reacting HN(R3)(R4) with a compound of formula IA:
- to give a compound of formula I:
- or a tautomer or pharmaceutically acceptable salt thereof;
- wherein:
- m is an integer from 1 to 3;
- n is an integer from 0 to 4;
- R1 is, independently at each occurrence, C1-C6alkyl, C1-C6alkoxy, halo, CF3, OCF3, hydroxy, C1-C5alkylC(O)O—, nitro, —CN, C2-C6alkenyl, C2-C6alkynyl, C6-C10aryl, C4-C10heteroaryl, C1-C6alkylS(O)—, C1-C6alkylS(O)2—, C1-C6alkylS(O)2NH—, C1-C6alkylS(O)2N(C1-C6alkyl)-, C6-C10arylS(O)2NH—, C6-C10arylS(O)2N(C1-C6alkyl)- C1-C5alkylC(O)NH—, C1-C5alkylC(O)N(C1-C6alkyl)-, or C6-C10arylC(O)NH—, C6-C10arylC(O)N(C1-C6alkyl)-;
- wherein each C6-C10aryl or C4-C10heteroaryl is independently substituted with 0-3 C1-C6alkyl, C1-C6alkoxy, halo, CF3, OCF3, hydroxy, C1-C5alkylC(O)O—, nitro, —CN, C2-C6alkenyl, or C2-C6alkynyl groups;
- and each C6-C10arylS(O)2NH—, C6-C10arylS(O)2N(C1-C6alkyl)- or C6-C10arylC(O)NH—, C6-C10arylC(O)N(C1-C6alkyl)- is independently substituted with 0-3 C1-C6alkyl, C1-C6alkoxy, halo, CF3, OCF3, hydroxy, C1-C5alkylC(O)O—, nitro, —CN, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkylS(O)—, C1-C6alkylS(O)2—, C1-C6alkylS(O)2NH—, C1-C6alkylS(O)2N(C1-C6alkyl)-, C1-C5alkylC(O)NH—, or C1-C5alkylC(O)N(C1-C6alkyl)- groups;
- R2 is C6-C10aryl or C4-C10heteroaryl substituted with 0-5 C1-C6alkyl, C1-C6alkoxy, halo, CF3, OCF3, hydroxy, C1-C5alkylC(O)O—, nitro, —CN, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkylS(O)—, C1-C6alkylS(O)2—, C1-C6alkylS(O)2NH—, C1-C6alkylS(O)2N(C1-C6alkyl)-, C6-C10arylS(O)2NH—, C6-C10arylS(O)2N(C1-C6alkyl)-, C1-C5alkylC(O)NH—, C1-C5alkylC(O)N(C1-C6alkyl)-, C6-C10arylC(O)NH—, C6-C10arylC(O)N(C1-C6alkyl)-, or C6-C10aryl or C4-C10heteroaryl optionally substituted with C1-C6alkyl, C1-C6alkoxy, halo, CF3, OCF3, hydroxy, C1-C5alkylC(O)O—, nitro, —CN, C2-C6alkenyl, or C2-C6alkynyl;
- R3 and R4 are, independently, H, C1-C6alkyl, C7-C16arylalkyl or (C4-C10heteroaryl)methyl, wherein each of C7-C16arylalkyl or (C4-C10heteroaryl)methyl are independently substituted with 0-3 C1-C6alkyl, C1-C6alkoxy, halo, CF3, OCF3, hydroxy, C1-C5alkylC(O)O—, nitro, —CN, C2-C6alkenyl, or C2-C6alkynyl groups;
- represents an S-isomer, R-isomer or racemate;
- wherein the compound of formula I is formed.
9 more elements
A process for the preparation of a compound of formula IA:
- or a tautomer or salt thereof;
- wherein:
- m is an integer from 1 to 3;
- n is an integer from 0 to 4;
- R1 is, independently at each occurrence, C1-C6alkyl, C1-C6alkoxy, halo, CF3, OCF3, hydroxy, C1-C5alkylC(O)O—, nitro, —CN, C2-C6alkenyl, C2-C6alkynyl, C6-C10aryl, C4-C10heteroaryl, C1-C6alkylS(O)—, C1-C6alkylS(O)2—, C1-C6alkylS(O)2NH—, C1-C6alkylS(O)2N(C1-C6alkyl)-, C6-C10arylS(O)2NH—, C6-C10arylS(O)2N(C1-C6alkyl)- C1-C5alkylC(O)NH—, C1-C5alkylC(O)N(C1-C6alkyl)-, or C6-C10arylC(O)NH—, C6-C10arylC(O)N(C1-C6alkyl)-;
- wherein each C6-C10aryl or C4-C10heteroaryl is independently substituted with 0-3 C1-C6alkyl, C1-C6alkoxy, halo, CF3, OCF3, hydroxy, C1-C5alkylC(O)O—, nitro, —CN, C2-C6alkenyl, or C2-C6alkynyl groups;
- and each C6-C10arylS(O)2NH—, C6-C10arylS(O)2N(C1-C6alkyl)- or C6-C10arylC(O)NH—, C6-C10arylC(O)N(C1-C6alkyl)- is independently substituted with 0-3 C1-C6alkyl, C1-C6alkoxy, halo, CF3, OCF3, hydroxy, C1-C5alkylC(O)O—, nitro, —CN, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkylS(O)—, C1-C6alkylS(O)2—, C1-C6alkylS(O)2NH—, C1-C6alkylS(O)2N(C1-C6alkyl)-, C1-C5alkylC(O)NH—, or C1-C5alkylC(O)N(C1-C6alkyl)- groups;
- R2 is C6-C10aryl or C4-C10heteroaryl substituted with 0-5 C1-C6alkyl, C1-C6alkoxy, halo, CF3, OCF3, hydroxy, C1-C5alkylC(O)O—, nitro, —CN, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkylS(O)—, C1-C6alkylS(O)2—, C1-C6alkylS(O)2NH—, C1-C6alkylS(O)2N(C1-C6alkyl)-, C6-C10arylS(O)2NH—, C6-C10arylS(O)2N(C1-C6alkyl)-, C1-C5alkylC(O)NH—, C1-C5alkylC(O)N(C1-C6alkyl)-, C6-C10arylC(O)NH—, C6-C10arylC(O)N(C1-C6alkyl)-, or C6-C10aryl or C4-C10heteroaryl optionally substituted with C1-C6alkyl, C1-C6alkoxy, halo, CF3, OCF3, hydroxy, C1-C5alkylC(O)O—, nitro, —CN, C2-C6alkenyl, or C2-C6alkynyl;
- and
- represents an S-isomer, R-isomer or racemate;
- the process comprising:
- reacting a compound of formula IB:
- in the presence of a base with a compound of formula IC:
- wherein Ga is an activating group.
11 more elements
Dependencies are inferred from the claim text.