Triethylamine → (S)-1-(4-(4-(4-(2-(tert-Butyldimethylsilyloxy)-1,1,1,3,3,3-hexafluoropropan-2-yl)benzyl)-piperazine-1-carbonyl)-2-fluorophenyl)-3-(1-hydroxybutan-2-yl)urea

HRID 1807724Notes

Reaction equation

HRID 1807724 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:15][CH2:14][N:13]([CH2:16][C:17]3[CH:22]=[CH:21][C:20]([C:23]([O:32][Si:33]([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34])([C:28]([F:31])([F:30])[F:29])[C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=3)[CH2:12][CH2:11]2)=[O:9])=[CH:4][C:3]=1[F:40].[C:41](Cl)(=O)[O:42]C1C=CC([N+]([O-])=O)=CC=1.[NH2:54][C@@H:55]([CH2:58][CH3:59])[CH2:56][OH:57].C(N(CC)CC)C>ClCCl>[Si:33]([O:32][C:23]([C:20]1[CH:19]=[CH:18][C:17]([CH2:16][N:13]2[CH2:14][CH2:15][N:10]([C:8]([C:5]3[CH:6]=[CH:7][C:2]([NH:1][C:41]([NH:54][C@@H:55]([CH2:58][CH3:59])[CH2:56][OH:57])=[O:42])=[C:3]([F:40])[CH:4]=3)=[O:9])[CH2:11][CH2:12]2)=[CH:22][CH:21]=1)([C:24]([F:25])([F:26])[F:27])[C:28]([F:31])([F:29])[F:30])([C:36]([CH3:37])([CH3:39])[CH3:38])([CH3:34])[CH3:35]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 821294-Nitrophenyl chloroformateHCID 1200842-Amino-1-butanol, (+)-HCID 59175907(4-Amino-3-fluorophenyl)(4-(4-(2-(tert-butyldimethylsilyloxy)-1,1,1,3,3,3-hexafluoropropan-2-yl)benzyl)piperazin-1-yl)methanone

Product 1

HCID 59175877(S)-1-(4-(4-(4-(2-(tert-Butyldimethylsilyloxy)-1,1,1,3,3,3-hexafluoropropan-2-yl)benzyl)-piperazine-1-carbonyl)-2-fluorophenyl)-3-(1-hydroxybutan-2-yl)ureaYield 72.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of (4-amino-3-fluorophenyl)(4-(4-(2-(tert-butyldimethylsilyloxy)-1,1,1,3,3,3-hexafluoropropan-2-yl)benzyl)piperazin-1-yl)methanone (0.421 mmol, 250 mg) and 4-nitrophenyl carbonochloridate (0.421 mmol, 85 mg) in dichloromethane (1 ml) was stirred at room temperature for 30 minutes. (S)-2-Aminobutan-1-ol (0.839 mmol, 0.079 mL, 74.8 mg) was added, followed by triethylamine (1.263 mmol, 0.176 mL, 128 mg) and the reaction stirred at room temperature overnight. The reaction mixture was diluted with dichloromethane (3 ml) and washed with saturated aqueous sodium hydrogen carbonate solution (5 ml). The organic phase was concentrated and the resulting residue was purified by column chromatography (2-5% methanol in dichloromethane) to afford the title compound (215 mg). MS (ESI) m/z 709.2 [M+H]+

Workup

  1. washwashed with saturated aqueous sodium hydrogen carbonate solution (5 ml)
  2. concentrationThe organic phase was concentrated
  3. customthe resulting residue was purified by column chromatography (2-5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-b4dc2c38334346e7a36cf17f2334f833
Source dataset
uspto-grants-2013_01
Patent number
US08357679B2

Reaction notes

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