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

HRID 445340Notes

Reaction equation

HRID 445340 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([F:10])=[C:6]([CH:9]=1)[C:7]#[N:8].[H-].[Na+].[F:13][C:14]([F:44])([F:43])[C:15]1[CH:20]=[CH:19][C:18]([C@@H:21]2[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH2:24][CH2:23][N:22]2[C:31](OC2C=CC([N+]([O-])=O)=CC=2)=[O:32])=[CH:17][CH:16]=1.O>C1COCC1.CO>[C:7]([C:6]1[CH:9]=[C:2]([NH:1][C:31]([N:22]2[CH2:23][CH2:24][C:25]3[C:30](=[CH:29][CH:28]=[CH:27][CH:26]=3)[C@H:21]2[C:18]2[CH:19]=[CH:20][C:15]([C:14]([F:43])([F:13])[F:44])=[CH:16][CH:17]=2)=[O:32])[CH:3]=[CH:4][C:5]=1[F:10])#[N:8]

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 27376735-Amino-2-fluorobenzonitrileHCID 59536297(R)-4-Nitrophenyl 1-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate

Product 1

HCID 59536324(R)-N-(3-Cyano-4-fluorophenyl)-1-(4-(trifluoromethyl)phenyl)-3,4-dihydro-isoquinoline-2(1H)-carboxamide

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 5-amino-2-fluorobenzonitrile (62 mg, 452 μmol) and sodium hydride, 60% dispersion in mineral oil (26 mg, 678 μmol) in THF (1.0 mL) was stirred at RT for 15 min. Then, (R)-4-nitrophenyl 1-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (100 mg, 226 μmol, example 88) was added and the mixture was stirred at RT for overnight. Then, a solution of H2O and MeOH (1:1, 0.2 mL) was added and the solvents were removed. The residue was then dissolved in a solution of DMSO and MeOH (1:1, 1 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 dissolved in MeOH (1 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 an orange solid. MS (ESI, positive ion) m/z: 440 (M+H).

Workup

  1. customthe solvents were removed
  2. dissolutionThe residue was then dissolved in a solution of DMSO and MeOH (1:1, 1 mL)
  3. customThe solution mixture was then purified by preparative HPLC (0%-100% MeCN 0.1% TFA/H2O 0.1% TFA)

Sources & evidence

ORD record
ord-2394235fc9e54306b053e878abef2057
Source dataset
uspto-grants-2013_07
Patent number
US08476297B2

Reaction notes

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