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

HRID 715887Notes

Reaction equation

HRID 715887 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([S:8][CH3:9])=[CH:4][N:3]=1.BrC1C=NC(Cl)=NC=1.[F:18][C:19]1([F:65])[CH2:24][CH2:23][CH:22]([C:25]2[C:34]3[CH:33]([O:35]CC4C=CC(OC)=CC=4)[CH2:32][C:31]([CH3:46])([CH3:45])[CH2:30][C:29]=3[N:28]=[C:27]([CH:47]3[CH2:52][CH2:51][NH:50][CH2:49][CH2:48]3)[C:26]=2[CH:53]([F:64])[C:54]2[CH:59]=[CH:58][C:57]([C:60]([F:63])([F:62])[F:61])=[CH:56][CH:55]=2)[CH2:21][CH2:20]1>>[F:65][C:19]1([F:18])[CH2:24][CH2:23][CH:22]([C:25]2[C:34]3[CH:33]([OH:35])[CH2:32][C:31]([CH3:45])([CH3:46])[CH2:30][C:29]=3[N:28]=[C:27]([CH:47]3[CH2:52][CH2:51][N:50]([C:2]4[N:7]=[CH:6][C:5]([S:8][CH3:9])=[CH:4][N:3]=4)[CH2:49][CH2:48]3)[C:26]=2[CH:53]([F:64])[C:54]2[CH:59]=[CH:58][C:57]([C:60]([F:62])([F:63])[F:61])=[CH:56][CH:55]=2)[CH2:21][CH2:20]1

Participants

4

Reactant 3

HCID 6066655-Bromo-2-chloropyrimidineHCID 219795322-Chloro-5-(methylthio)pyrimidineHCID 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 86682467(-)-4-(4,4-Difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-7,7-dimethyl-2-[1-(5-methylthiopyrimidin-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-methylthiopyrimidine, which was prepared by a method similar to that of Reference Example 36, instead of 5-bromo-2-chloropyrimidine, and from 60 mg (89 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, 50 mg of the title compound was obtained as a white solid (yield: 84%).

Workup

  1. customwas prepared by a method similar to that of Reference Example 36

Sources & evidence

ORD record
ord-6db5f363b45942189ed9a85bb781393b
Source dataset
uspto-grants-2015_11
Patent number
US09187450B2

Reaction notes

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