Dimethylformamide → (1S,2S)-N-(7-bromoisoquinolin-3-yl)-2-fluorocyclopropanecarboxamide
Reaction equation
[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH2:12])[N:8]=[CH:9]2)=[CH:4][CH:3]=1.[F:13][C@H:14]1[CH2:16][C@H:15]1[C:17](O)=[O:18].F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.CN(C)C=O>CN(C)C1C=CN=CC=1.C(OCC)(=O)C>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH:12][C:17]([C@@H:15]3[CH2:16][C@@H:14]3[F:13])=[O:18])[N:8]=[CH:9]2)=[CH:4][CH:3]=1Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 50 °C
Procedure
A mixture of 7-bromoisoquinolin-3-amine (4.531 g, 20.31 mmol), (1S,2S)-2-fluorocyclopropanecarboxylic acid (2.002 g, 19.24 mmol), (7-azabenzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (12.148 g, 23.433 mmol), N,N-diisopropylethylamine (8.50 mL, 48.8 mmol), 4-dimethylaminopyridine (0.245 g, 2.00 mmol), and N,N-dimethylformamide (100 mL, 1000 mmol) was stirred at 50° C. for 18 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate, washed with water and brine, dried over MgSO4, filtered, and concentrated. The crude residue was purified via flash chromatography on silica gel (120 g silica, solvent gradient: 0-30% ethyl acetate in dichloromethane) to yield 6.5208 g of the title compound. LCMS (ESI): M+H=309.2.
Workup
- temperatureThe reaction mixture was cooled to room temperature
- washwashed with water and brine
- dry with materialdried over MgSO4
- filtrationfiltered
- concentrationconcentrated
- customThe crude residue was purified via flash chromatography on silica gel (120 g silica, solvent gradient: 0-30% ethyl acetate in dichloromethane)
Sources & evidence
- ORD record
- ord-eb6a3293b0f14589876790723beeb863
- Source dataset
- uspto-grants-2015_12
- Patent number
- US09206175B2
Reaction notes
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