5-Bromo-2-chloropyrimidine → (-)-4-(4,4-Difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-7,7-dimethyl-2-{1-[5-(methylsulphonyl)pyrimidin-2-yl]piperidin-4-yl}-5,6,7,8-tetrahydroquinolin-5-ol

HRID 715888Notes

Reaction equation

HRID 715888 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([S:8]([CH3:11])(=[O:10])=[O:9])=[CH:4][N:3]=1.BrC1C=NC(Cl)=NC=1.[F:20][C:21]1([F:67])[CH2:26][CH2:25][CH:24]([C:27]2[C:36]3[CH:35]([O:37]CC4C=CC(OC)=CC=4)[CH2:34][C:33]([CH3:48])([CH3:47])[CH2:32][C:31]=3[N:30]=[C:29]([CH:49]3[CH2:54][CH2:53][NH:52][CH2:51][CH2:50]3)[C:28]=2[CH:55]([F:66])[C:56]2[CH:61]=[CH:60][C:59]([C:62]([F:65])([F:64])[F:63])=[CH:58][CH:57]=2)[CH2:23][CH2:22]1>>[F:67][C:21]1([F:20])[CH2:26][CH2:25][CH:24]([C:27]2[C:36]3[CH:35]([OH:37])[CH2:34][C:33]([CH3:47])([CH3:48])[CH2:32][C:31]=3[N:30]=[C:29]([CH:49]3[CH2:54][CH2:53][N:52]([C:2]4[N:7]=[CH:6][C:5]([S:8]([CH3:11])(=[O:10])=[O:9])=[CH:4][N:3]=4)[CH2:51][CH2:50]3)[C:28]=2[CH:55]([F:66])[C:56]2[CH:61]=[CH:60][C:59]([C:62]([F:64])([F:65])[F:63])=[CH:58][CH:57]=2)[CH2:23][CH2:22]1

Participants

4

Reactant 3

HCID 6066655-Bromo-2-chloropyrimidineHCID 156534822-Chloro-5-methanesulfonylpyrimidineHCID 86682426(-)-4-(4,4-Difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-5-[(4-methoxybenzyl)oxy]-7,7-dimethyl-2-(piperidin-4-yl)-5,6,7,8-tetrahydroquinoline

Product 1

HCID 86682468(-)-4-(4,4-Difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-7,7-dimethyl-2-{1-[5-(methylsulphonyl)pyrimidin-2-yl]piperidin-4-yl}-5,6,7,8-tetrahydroquinolin-5-ol

Procedure

Reactions similar to those of the first step of Example 2 and Example 38 were performed except for using 2-chloro-5-(methylsulfonyl)pyrimidine, which was prepared by a method similar to that of Reference Example 14, instead of 5-bromo-2-chloropyrimidine, and from 49 mg (72 μmol) of (−)-4-(4,4-Difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-5-[(4-methoxybenzyl)oxy]-7,7-dimethyl-2-(piperidin-4-yl)-5,6,7,8-tetrahydroquinoline, which was prepared by a method similar to that of Reference Example 10, 45 mg of the title compound was obtained as a white solid (yield: 88%).

Workup

  1. customwas prepared by a method similar to that of Reference Example 14

Sources & evidence

ORD record
ord-879dc2a736914522a802635b5cebdfb8
Source dataset
uspto-grants-2015_11
Patent number
US09187450B2

Reaction notes

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