US2010036125A1PendingUtilityA1
Synthesis of ccr5 receptor antagonists
Est. expiryJan 6, 2025(expired)· nominal 20-yr term from priority
Inventors:Xiongwei ShiMan ZhuWilliam W. LeongVilas Hareshwar DahanukarIlia ZavialovCecilia ProiettiShannon ZhaoHong-Chang LeeYi LiuHoa N. NguyenWenxue WuBosco D'SaFeng LiangLoc Thanh Tran
A61P 37/06A61P 31/18A61P 43/00A61P 37/08A61P 25/00A61P 29/00C07D 211/26C07D 211/96C07D 401/14A61P 1/04A61P 11/06A61P 17/02A61P 17/06A61P 19/02
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Claims
Abstract
The present invention is directed to the synthesis of 4-[4-[(R)-[1-[cyclopropylsulfonyl)-4-piperidinyl](3-fluorophenyl)methyl]-3(S)-methyl- 1 -piperazinyl]-1-[(4,6-dimethyl-5-pyrimidinyl)carbonyl]-4-methylpiperidine], and intermediates therefor from readily available starting materials by a novel route.
Claims
exact text as granted — not AI-modified1 . A process for preparing a compound of formula (V)
where PMB is p-methoxybenzyl and Cbz is carbobenzyloxy from a compound of formula (IV):
said process comprising reacting said compound of formula IV with a reagent selected from (i) benzotriazole, a nitrites, a halogen, an alkylsulfonate or a haloalkyl ester (ii) 3-fluorophenylmagnesium bromide; and (iii) the compound:
in a suitable solvent to yield a compound of formula V.
2 . A process for preparing a compound of formula VI:
from a compound of formula V:
where PMB is p-methoxybenzyl and Cbz is carbobenzyloxy, said process comprising removing the PMB protecting group of the compound of formula V to produce a compound of formula VI.
3 . A process for preparing a compound of formula VII
where Cbz is carbobenzyloxy, from a compound of formula VI:
said process comprising sulfonylating the compound of formula VI with cyclopropyl sulfonyl chloride to form the compound of formula VIII.
4 . The process for preparing a compound of formula VIII:
from a compound of formula VIII:
where Cbz is carbobenzyloxy, said process comprising removing the Cbz protecting group from the compound of formula VII and reacting with hydrogen bromide to produce the di-hydrobromide salt formula VIII.
5 . The process of claim 1 wherein said solvent is selected from the group consisting of hydrocarbon, ether, and mixtures thereof.
6 . The process of claim 1 wherein said reagent is benzotriazole.
7 . The process of claim 2 wherein removal of said PMB protecting group is accomplished with trifluoroacetic anhydride.
8 . The process of claim 3 wherein said sulfonylating step is performed in toluene and utilizing triethyl amine as the base.
9 . The process of claim 4 wherein removal of said Cbz is accomplished using methanesulfonic acid.
10 . A compound of the formula:
where PMB is p-methoxybenzyl and Cbz is carbobenzyloxy, including isomers of said compound.
11 . A compound of the formula:
where Cbz is carbobenzyloxy, including isomers of said compound.
12 . A compound of the formula:
where Cbz is carbobenzyloxy, including isomers of said compound.
13 . A compound of the formula:
including isomers of said compound.
14 . A compound of the formula:
including isomers of said compound.
15 . A compound of the formula:
including isomers of said compound.
16 . A compound of the formula:
including isomers of said compound.Cited by (0)
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