Diisopropylethylamine → t-Butyl 4-(3-(1-(3,5-dichlorophenyl)ethylamino)-4-(2,2,2-trifluoroacetyl)phenyl)piperazine-1-carboxylate
Reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]([NH:11][C:12]2[CH:17]=[C:16](F)[CH:15]=[CH:14][C:13]=2[C:19](=[O:24])[C:20]([F:23])([F:22])[F:21])[CH3:10])[CH:5]=[C:6]([Cl:8])[CH:7]=1.[N:25]1([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1.C(N(CC)C(C)C)(C)C>C(#N)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]([NH:11][C:12]2[CH:17]=[C:16]([N:28]3[CH2:27][CH2:26][N:25]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:30][CH2:29]3)[CH:15]=[CH:14][C:13]=2[C:19](=[O:24])[C:20]([F:23])([F:22])[F:21])[CH3:10])[CH:5]=[C:6]([Cl:8])[CH:7]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
1-(2-(1-(3,5-Dichlorophenyl)ethylamino)-4-fluorophenyl)-2,2,2-trifluoroethanone (600 mg, 1.62 mmol), t-butyl piperazine-1-carboxylate (110 mg, 0.29 mmol), N,N-diisopropylethylamine (74.6 mg, 0.58 mmol) were stirred at 60° C. in dry acetonitrile (20 mL) for 3 days. The solvent was evaporated and the residue was dissolved in dichloromethane and washed with water. The dichloromethane was evaporated and the crude compound was purified by silica chromatography using 20% ethyl acetate in hexanes to afford the title compound (77.0 mg, 49% yield). 1H NMR (400 MHz, CDCl3): δ 9.31 (d, 1H), 7.63 (d, 1H), 7.25 (s, 1H), 7.22 (s, 2H), 6.18 (d, 1H), 5.53 (s, 1H), 4.48 (m, 1H), 3.48 (m, 4H), 3.25 (m, 4H), 1.60 (d, 3H), 1.47 (s, 9H); MS (ESI) m/z: Calculated for C25H28Cl2F3N3O3: 545.15; Observed: 568.4 (M++Na).
Workup
- customThe solvent was evaporated
- dissolutionthe residue was dissolved in dichloromethane
- washwashed with water
- customThe dichloromethane was evaporated
- customthe crude compound was purified by silica chromatography
Sources & evidence
- ORD record
- ord-3cfffd91ae534e0c91c691865549a69b
- Source dataset
- uspto-grants-2011_06
- Patent number
- US07968538B2
Reaction notes
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