Water → (R)-N-(4-Cyano-3-fluorophenyl)-1-(4-(trifluoromethyl)phenyl)-3,4-dihydro-isoquinoline-2(1H)-carboxamide

HRID 445337Notes

Reaction equation

HRID 445337 reaction equation
[F:1][C:2]([F:32])([F:31])[C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH2:12][CH2:11][N:10]2[C:19](OC2C=CC([N+]([O-])=O)=CC=2)=[O:20])=[CH:5][CH:4]=1.[NH2:33][C:34]1[CH:41]=[CH:40][C:37]([C:38]#[N:39])=[C:36]([F:42])[CH:35]=1.[H-].[Na+].O>CC#N>[C:38]([C:37]1[CH:40]=[CH:41][C:34]([NH:33][C:19]([N:10]2[CH2:11][CH2:12][C:13]3[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=3)[C@H:9]2[C:6]2[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:32])[F:31])=[CH:8][CH:7]=2)=[O:20])=[CH:35][C:36]=1[F:42])#[N:39]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 27834134-Amino-2-fluorobenzonitrileHCID 59536297(R)-4-Nitrophenyl 1-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate

Product 1

HCID 59536432(R)-N-(4-Cyano-3-fluorophenyl)-1-(4-(trifluoromethyl)phenyl)-3,4-dihydro-isoquinoline-2(1H)-carboxamide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of (R)-4-nitrophenyl 1-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (70 mg, 158 μmol, example 88) in MeCN (0.5 mL) was added 4-amino-2-fluorobenzonitrile (65 mg, 475 μmol). The resulting mixture was then subjected to a microwave irradiation at 180° C. for 15 min. Then, sodium hydride, 60% dispersion in mineral oil (22 μL, 475 μmol) was added and the mixture was stirred at RT for overnight. Then, H2O (0.5 mL) was added and the solvents were removed. The residue was then dissolved in a solution of MeOH and DMSO (1:1, 1.0 mL). The solution mixture was then purified by preparative HPLC (0%-100% MeCN 0.1% TFA/H2O 0.1% TFA) to give the desired product, which was then dissolved in MeOH (1.0 mL). The solution was then washed through PL-HCO3 MP resin (polymerlabs, 200 mg/6 mL tube) and the resin was washed with MeOH (2×0.5 mL). The combined washings were then concentrated and dried under vacuum to give the title compound as a yellow solid. MS (ESI, positive ion) m/z: 440 (M+H).

Workup

  1. customThe resulting mixture was then subjected to a microwave irradiation at 180° C. for 15 min
  2. customthe solvents were removed
  3. dissolutionThe residue was then dissolved in a solution of MeOH and DMSO (1:1, 1.0 mL)
  4. customThe solution mixture was then purified by preparative HPLC (0%-100% MeCN 0.1% TFA/H2O 0.1% TFA)

Sources & evidence

ORD record
ord-3fbe7209ba814195a92382a6a5a58ac8
Source dataset
uspto-grants-2013_07
Patent number
US08476297B2

Reaction notes

Loading…