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

HRID 632599Notes

Reaction equation

[CH3:1][S:2]([OH:5])(=[O:4])=[O:3].C(OC(C)C)(=O)C.[F:13][C:14]1([F:65])[CH2:19][CH2:18][CH:17]([C:20]2[C:29]3[C@@H:28](O)[CH2:27][C:26]([CH3:32])([CH3:31])[CH2:25][C:24]=3[N:23]=[C:22]([CH:33]3[CH2:38][CH2:37][N:36]([C:39]4[N:44]=[CH:43][C:42]([O:45][CH2:46][CH2:47][CH2:48][S:49]([CH3:52])(=[O:51])=[O:50])=[CH:41][N:40]=4)[CH2:35][CH2:34]3)[C:21]=2[C@@H: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)[CH2:16][CH2:15]1>>[CH3:1][S:2]([O:5][C@H:28]1[CH2:27][C:26]([CH3:31])([CH3:32])[CH2:25][C:24]2[N:23]=[C:22]([CH:33]3[CH2:34][CH2:35][N:36]([C:39]4[N:40]=[CH:41][C:42]([O:45][CH2:46][CH2:47][CH2:48][S:49]([CH3:52])(=[O:50])=[O:51])=[CH:43][N:44]=4)[CH2:37][CH2:38]3)[C:21]([C@@H:53]([F:64])[C:54]3[CH:55]=[CH:56][C:57]([C:60]([F:62])([F:61])[F:63])=[CH:58][CH:59]=3)=[C:20]([CH:17]3[CH2:18][CH2:19][C:14]([F:65])([F:13])[CH2:15][CH2:16]3)[C:29]1=2)(=[O:4])=[O:3]

Participants

Reactant 3

HCID 6395Methanesulfonic Acid

HCID 7915Isopropyl Acetate

HCID 71604910HCID 71604910, compound

Product 1

HCID 118451733(5S)-4-(4,4-Difluorocyclohexyl)-3-{(S)-fluoro[4-(trifluoromethyl)phenyl]methyl}-7,7-dimethyl-2-(1-{5-[3-(methylsulfonyl)propoxy]pyrimidin-2-yl}piperidin-4-yl)-5,6,7,8-tetrahydroquinolin-5-ol methanesulfonateYield 80.2%

Procedure

Reactions similar to those of Example 13 were performed except for using 3.8 μl (57 μmol) of methanesulfonic acid instead of 35% hydrochloric acid and using 1.5 ml of isopropyl acetate instead of acetone, and from 40.0 mg (52.0 μmol) of (5S)-4-(4,4-Difluorocyclohexyl)-3-{(S)-fluoro[4-(trifluoromethyl)phenyl]methyl}-7,7-dimethyl-2-(1-{5-[3-(methylsulfonyl)propoxy]pyrimidin-2-yl}piperidin-4-yl)-5,6,7,8-tetrahydroquinolin-5-ol, which was prepared by a method similar to that of Reference Example 28, 35.3 mg of the title compound was obtained as a white powder (yield: 78%).

Sources & evidence

ORD record: ord-75923584adc44f9e91f43f097742270b
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09321747B2

Reaction notes

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