Acetic Acid → 1,1,1-trifluoro-2-(4-((2S)-2-((methyl((1-methyl-1H-imidazol-4-yl)methyl)amino)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanol

HRID 1972493Notes

Reaction equation

HRID 1972493 reaction equation
[F:1][C:2]([F:30])([F:29])[C:3]([C:6]1[CH:11]=[CH:10][C:9]([N:12]2[CH2:17][CH2:16][N:15]([S:18]([C:21]3[S:22][CH:23]=[CH:24][CH:25]=3)(=[O:20])=[O:19])[CH2:14][C@@H:13]2[CH2:26][NH:27][CH3:28])=[CH:8][CH:7]=1)([OH:5])[CH3:4].[CH3:31][N:32]1[CH:36]=[C:35]([CH:37]=O)[N:34]=[CH:33]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].CC(O)=O>CO.ClCCCl>[F:30][C:2]([F:1])([F:29])[C:3]([C:6]1[CH:11]=[CH:10][C:9]([N:12]2[CH2:17][CH2:16][N:15]([S:18]([C:21]3[S:22][CH:23]=[CH:24][CH:25]=3)(=[O:19])=[O:20])[CH2:14][C@@H:13]2[CH2:26][N:27]([CH3:28])[CH2:37][C:35]2[N:34]=[CH:33][N:32]([CH3:31])[CH:36]=2)=[CH:8][CH:7]=1)([OH:5])[CH3:4]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 5734191-Methyl-1H-imidazole-4-carbaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 665828171,1,1-trifluoro-2-(4-((2S)-2-((methylamino)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanol

Product 1

HCID 569325191,1,1-trifluoro-2-(4-((2S)-2-((methyl((1-methyl-1H-imidazol-4-yl)methyl)amino)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanolYield 33.2%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 887MethanolSolvent

Procedure

A 25-mL round-bottomed flask was charged with 1,1,1-trifluoro-2-(4-((2S)-2-((methylamino)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanol (50 mg, 0.108 mmol), 1-methyl-1H-imidazole-4-carbaldehyde (59.4 mg, 0.539 mmol, ASDI, Newark, Del.), sodium triacetoxyborohydride (114 mg, 0.539 mmol, Sigma-Aldrich, St. Louis, Mo.), AcOH (0.617 μl, 10.79 μmol) and DCE (5 mL). The reaction was stirred at room temperature for 12 h. MeOH (20 mL), was added and the mixture was concentrated onto silica gel and purified via column chromatography (12 g silica gel, 5 to 10% CH2Cl2 in MeOH) to give 1,1,1-trifluoro-2-(4-((2S)-2-((methyl((1-methyl-1H-imidazol-4-yl)methyl)amino)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanol (20 mg) as a mixture of two isomers.

Workup

  1. concentrationthe mixture was concentrated onto silica gel
  2. custompurified via column chromatography (12 g silica gel, 5 to 10% CH2Cl2 in MeOH)

Sources & evidence

ORD record
ord-dcd94155c6694ac2b9499e29edfb6e58
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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