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

HRID 715851Notes

Reaction equation

HRID 715851 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.Br[C:9]1[CH:10]=[N:11][C:12]([N:15]2[CH2:20][CH2:19][CH:18]([C:21]3[C:30]([CH:31]([F:42])[C:32]4[CH:37]=[CH:36][C:35]([C:38]([F:41])([F:40])[F:39])=[CH:34][CH:33]=4)=[C:29]([CH:43]4[CH2:48][CH2:47][C:46]([F:50])([F:49])[CH2:45][CH2:44]4)[C:28]4[CH:27]([O:51]CC5C=CC(OC)=CC=5)[CH2:26][C:25]([CH3:62])([CH3:61])[CH2:24][C:23]=4[N:22]=3)[CH2:17][CH2:16]2)=[N:13][CH:14]=1>>[F:50][C:46]1([F:49])[CH2:47][CH2:48][CH:43]([C:29]2[C:28]3[CH:27]([OH:51])[CH2:26][C:25]([CH3:61])([CH3:62])[CH2:24][C:23]=3[N:22]=[C:21]([CH:18]3[CH2:19][CH2:20][N:15]([C:12]4[N:13]=[CH:14][C:9]([N:5]5[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]5)=[CH:10][N:11]=4)[CH2:16][CH2:17]3)[C:30]=2[CH:31]([F:42])[C:32]2[CH:33]=[CH:34][C:35]([C:38]([F:40])([F:41])[F:39])=[CH:36][CH:37]=2)[CH2:44][CH2:45]1

Participants

3

Reactant 2

HCID 531671-MethylpiperazineHCID 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 76372312(-)-4-(4,4-Difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-7,7-dimethyl-2-{1-[5-(4-methylpiperazin-1-yl)pyrimidin-2-yl]piperidin-4-yl}-5,6,7,8-tetrahydroquinolin-5-ol

Procedure

Reactions similar to those of the first step of Example 5 and Example 7 were performed except for using 1-methyl piperazine instead of morpholine, and from 120 mg (0.144 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, 36 mg of the title compound was obtained as a light yellow solid (yield: 34%).

Sources & evidence

ORD record
ord-495aa2e956ab433090d2391cae0e449f
Source dataset
uspto-grants-2015_11
Patent number
US09187450B2

Reaction notes

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