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

HRID 715878Notes

Reaction equation

HRID 715878 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([O:8][C@@H:9]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10]2)=[CH:4][N:3]=1.ClC1N=CC(OC2CCN(C)CC2)=CN=1.[F:30][C:31]1([F:77])[CH2:36][CH2:35][CH:34]([C:37]2[C:46]3[CH:45]([O:47]CC4C=CC(OC)=CC=4)[CH2:44][C:43]([CH3:58])([CH3:57])[CH2:42][C:41]=3[N:40]=[C:39]([CH:59]3[CH2:64][CH2:63][NH:62][CH2:61][CH2:60]3)[C:38]=2[CH:65]([F:76])[C:66]2[CH:71]=[CH:70][C:69]([C:72]([F:75])([F:74])[F:73])=[CH:68][CH:67]=2)[CH2:33][CH2:32]1>>[F:77][C:31]1([F:30])[CH2:36][CH2:35][CH:34]([C:37]2[C:46]3[CH:45]([OH:47])[CH2:44][C:43]([CH3:57])([CH3:58])[CH2:42][C:41]=3[N:40]=[C:39]([CH:59]3[CH2:64][CH2:63][N:62]([C:2]4[N:7]=[CH:6][C:5]([O:8][C@@H:9]5[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10]5)=[CH:4][N:3]=4)[CH2:61][CH2:60]3)[C:38]=2[CH:65]([F:76])[C:66]2[CH:71]=[CH:70][C:69]([C:72]([F:74])([F:75])[F:73])=[CH:68][CH:67]=2)[CH2:33][CH2:32]1

Participants

4

Reactant 3

HCID 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-tetrahydroquinolineHCID 866824582-chloro-5-{[(3R)-1-methylpyrrolidin-3-yl]oxy}pyrimidineHCID 866824592-Chloro-5-[(1-methylpiperidin-4-yl)oxy]pyrimidine

Product 1

HCID 866824574-(4,4-Difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-7,7-dimethyl-2-[1-(5-{[(3R)-1-methylpyrrolidin-3-yl]oxy}pyrimidin-2-yl)piperidin-4-yl]-5,6,7,8-tetrahydroquinolin-5-ol

Procedure

Reactions similar to those of Reference Example 29 and Example 38 were performed except for using 2-chloro-5-{[(3R)-1-methylpyrrolidin-3-yl]oxy}pyrimidine, which was prepared by a method similar to that of Reference Example 30, instead of 2-chloro-5-[(1-methylpiperidin-4-yl)oxy]pyrimidine, and from 100 mg (0.155 mmol) 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, 58 mg of the title compound was obtained as a white solid (yield: 44%).

Workup

  1. customwas prepared by a method similar to that of Reference Example 30

Sources & evidence

ORD record
ord-57847d8807184f3c909436d272d7f19c
Source dataset
uspto-grants-2015_11
Patent number
US09187450B2

Reaction notes

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