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

HRID 715890Notes

Reaction equation

HRID 715890 reaction equation
[NH:1]1[CH2:5][CH2:4][C@H:3]([OH:6])[CH2:2]1.Br[C:8]1[CH:9]=[N:10][C:11]([N:14]2[CH2:19][CH2:18][CH:17]([C:20]3[C:29]([CH:30]([F:41])[C:31]4[CH:36]=[CH:35][C:34]([C:37]([F:40])([F:39])[F:38])=[CH:33][CH:32]=4)=[C:28]([CH:42]4[CH2:47][CH2:46][C:45]([F:49])([F:48])[CH2:44][CH2:43]4)[C:27]4[CH:26]([O:50]CC5C=CC(OC)=CC=5)[CH2:25][C:24]([CH3:61])([CH3:60])[CH2:23][C:22]=4[N:21]=3)[CH2:16][CH2:15]2)=[N:12][CH:13]=1>>[F:49][C:45]1([F:48])[CH2:44][CH2:43][CH:42]([C:28]2[C:27]3[CH:26]([OH:50])[CH2:25][C:24]([CH3:60])([CH3:61])[CH2:23][C:22]=3[N:21]=[C:20]([CH:17]3[CH2:16][CH2:15][N:14]([C:11]4[N:12]=[CH:13][C:8]([N:1]5[CH2:5][CH2:4][C@H:3]([OH:6])[CH2:2]5)=[CH:9][N:10]=4)[CH2:19][CH2:18]3)[C:29]=2[CH:30]([F:41])[C:31]2[CH:32]=[CH:33][C:34]([C:37]([F:38])([F:40])[F:39])=[CH:35][CH:36]=2)[CH2:47][CH2:46]1

Participants

3

Reactant 2

HCID 2733874(3S)-pyrrolidin-3-olHCID 866824252-[1-(5-Bromopyrimidin-2-yl)piperidin-4-yl]-4-(4,4-difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-5-[(4-methoxybenzyl)oxy]-7,7-dimethyl-5,6,7,8-tetrahydroquinoline

Product 1

HCID 86682470(-)-4-(4,4-Difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-2-(1-{5-[(3S)-3-hydroxypyrrolidin-1-yl]pyrimidin-2-yl}piperidin-4-yl)-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-5-ol

Procedure

Reactions similar to those of Reference Example 13 were performed except for using (3S)-3-pyrrolidinol instead of isonipecotic acid ethyl ester, and from 100 mg (0.120 mmol) of (−)-2-[1-(5-Bromopyrimidin-2-yl)piperidin-4-yl]-4-(4,4-difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-5-[(4-methoxybenzyl)oxy]-7,7-dimethyl-5,6,7,8-tetrahydroquinoline, which was prepared by a method similar to that of Reference Example 11, 56 mg of the title compound was obtained as a white solid (yield: 65%).

Sources & evidence

ORD record
ord-8e858f9fba264403a9f7857f2d7e7801
Source dataset
uspto-grants-2015_11
Patent number
US09187450B2

Reaction notes

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