Aniline → 1,1,1-trifluoro-2-(4-((2S)-2-((phenylamino)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanol

HRID 1972580Notes

Reaction equation

CS(O[CH2:6][C@H:7]1[CH2:12][N:11]([S:13]([C:16]2[S:17][CH:18]=[CH:19][CH:20]=2)(=[O:15])=[O:14])[CH2:10][CH2:9][N:8]1[C:21]1[CH:26]=[CH:25][C:24]([C:27]([OH:33])([CH3:32])[C:28]([F:31])([F:30])[F:29])=[CH:23][CH:22]=1)(=O)=O.[NH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>CO>[F:29][C:28]([F:30])([F:31])[C:27]([C:24]1[CH:25]=[CH:26][C:21]([N:8]2[CH2:9][CH2:10][N:11]([S:13]([C:16]3[S:17][CH:18]=[CH:19][CH:20]=3)(=[O:15])=[O:14])[CH2:12][C@@H:7]2[CH2:6][NH:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)=[CH:22][CH:23]=1)([OH:33])[CH3:32]

Participants

Conditions

Temperature: 140 °C

Procedure

A 20-mL microwave vial was charged with ((2R)-4-(thiophen-2-ylsulfonyl)-1-(4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)phenyl)piperazin-2-yl)methyl methanesulfonate (0.500 g, 0.946 mmol, Intermediate B), aniline (0.884 g, 9.46 mmol), and MeOH (8.0 mL). The vial was sealed and heated in an Initiator microwave reactor (Biotage AB, Inc., Uppsala, Sweden) at 140° C. for 30 min. After cooling to room temperature, the reaction mixture was concentrated and the crude product was purified by column chromatography (80 g, 2 to 5% 2M NH3 in MeOH/CH2Cl2) to afford 1,1,1-trifluoro-2-(4-((2S)-2-((phenylamino)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanol (0.285 g) as a mixture of two isomers.

Workup

customThe vial was sealed
temperatureAfter cooling to room temperature
concentrationthe reaction mixture was concentrated
customthe crude product was purified by column chromatography (80 g, 2 to 5% 2M NH3 in MeOH/CH2Cl2)

Sources & evidence

ORD record: ord-76c4ec1399bb4967b9b80db992e92eea
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08431563B2

Reaction notes

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