1-Chloro-4-isocyanato-2-(trifluoromethyl) benzene → 1-(2-(2-amino-5-(1-(3-((tert-butyldimethylsilyl)oxy)propyl)-1H-tetrazol-5-yl)pyridin-3-yl)benzo[b]thiophen-5-yl)-3-(4-chloro-3-(trifluoromethyl)phenyl)urea

HRID 2199622Notes

Reaction equation

HRID 2199622 reaction equation
[NH2:1][C:2]1[CH:33]=[CH:32][C:5]2[S:6][C:7]([C:9]3[C:10]([NH2:31])=[N:11][CH:12]=[C:13]([C:15]4[N:19]([CH2:20][CH2:21][CH2:22][O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[N:18]=[N:17][N:16]=4)[CH:14]=3)=[CH:8][C:4]=2[CH:3]=1.[Cl:34][C:35]1[CH:40]=[CH:39][C:38]([N:41]=[C:42]=[O:43])=[CH:37][C:36]=1[C:44]([F:47])([F:46])[F:45]>O1CCCC1.C(OCC)(=O)C>[NH2:31][C:10]1[C:9]([C:7]2[S:6][C:5]3[CH:32]=[CH:33][C:2]([NH:1][C:42]([NH:41][C:38]4[CH:39]=[CH:40][C:35]([Cl:34])=[C:36]([C:44]([F:46])([F:45])[F:47])[CH:37]=4)=[O:43])=[CH:3][C:4]=3[CH:8]=2)=[CH:14][C:13]([C:15]2[N:19]([CH2:20][CH2:21][CH2:22][O:23][Si:24]([C:27]([CH3:28])([CH3:29])[CH3:30])([CH3:25])[CH3:26])[N:18]=[N:17][N:16]=2)=[CH:12][N:11]=1

Participants

5

Reactant 2

HCID 27332651-Chloro-4-isocyanato-2-(trifluoromethyl) benzeneHCID 1317356943-(5-aminobenzo[b]thiophen-2-yl)-5-(1-(3-((tert-butyldimethylsilyl)oxy)propyl)-1H-tetrazol-5-yl)pyridin-2-amine

Product 1

HCID 1317356961-(2-(2-amino-5-(1-(3-((tert-butyldimethylsilyl)oxy)propyl)-1H-tetrazol-5-yl)pyridin-3-yl)benzo[b]thiophen-5-yl)-3-(4-chloro-3-(trifluoromethyl)phenyl)urea

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To the stirring solution of 3-(5-aminobenzo[b]thiophen-2-yl)-5-(1-(3-((tert-butyldimethylsilyl)oxy)propyl)-1H-tetrazol-5-yl)pyridin-2-amine (123 mg, 0.256 mmol, 1 eq) in anhydrous tetrahydrofuran (3 mL) under nitrogen atmosphere was added 4-chloro-3-(trifluoromethyl)phenyl isocyanate (58 mg, 1 eq) and the reaction mixture was stirred at room temperature for three hours. The reaction was then diluted with ethyl acetate, washed sequentially with aqueous ammonium chloride, saturated aqueous sodium bicarbonate, and brine, and dried with anhydrous sodium sulfate. The upper clear solution was decanted and concentrated under reduced pressure and loaded onto silica. The mixture was subject to a gradient column chromatography (EtOAc-Hex 1:5 to 2:1) to give 1-(2-(2-amino-5-(1-(3-((tert-butyldimethylsilyl)oxy)propyl)-1H-tetrazol-5-yl)pyridin-3-yl)benzo[b]thiophen-5-yl)-3-(4-chloro-3-(trifluoromethyl)phenyl)urea as a white solid in the amount of 130 mg.

Workup

  1. washwashed sequentially with aqueous ammonium chloride, saturated aqueous sodium bicarbonate, and brine
  2. dry with materialdried with anhydrous sodium sulfate
  3. customThe upper clear solution was decanted
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d694df39eed646ae9bdde48387d17bd0
Source dataset
uspto-grants-2016_06
Patent number
US09359336B2

Reaction notes

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