Isopropylamine → HCID 66582708, compound

HRID 1972571Notes

Reaction equation

HRID 1972571 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.[CH:34]([NH2:37])([CH3:36])[CH3:35]>CO>[NH3:8].[F:30][C:28]([F:31])([F:29])[C:27]([C:24]1[CH:23]=[CH:22][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:14])=[O:15])[CH2:12][C@@H:7]2[CH2:6][NH:37][CH:34]([CH3:36])[CH3:35])=[CH:26][CH:25]=1)([OH:33])[CH3:32]

Participants

5

Reactant 2

HCID 6363IsopropylamineHCID 86670301((2R)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl methanesulfonate2×

Product 2

HCID 222AmmoniaYield 2%HCID 66582708HCID 66582708, compoundYield 154.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
140 °C

Procedure

To a 20 mL of microwave vial was added ((2R)-4-(thiophen-2-ylsulfonyl)-1-(4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)phenyl)piperazin-2-yl)methyl methanesulfonate (1.0 g, 1.9 mmol, Intermediate B), isopropylamine (2.5 mL, 28 mmol, Aldrich, St. Louis, Mo.), and MeOH (10.0 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 of silica gel, 100% CH2Cl2 first then 2 to 5% 2M NH3 in MeOH/CH2Cl2) to afford 1,1,1-trifluoro-2-(4-((2S)-2-(((1-methylethyl)amino)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanol (0.720 g) as a white foam.

Workup

  1. customThe vial was sealed
  2. temperatureAfter cooling to room temperature
  3. concentrationthe reaction mixture was concentrated
  4. customthe crude product was purified by column chromatography (80 g of silica gel, 100% CH2Cl2 first

Sources & evidence

ORD record
ord-d07253b8858843859d08e6d6c970351e
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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