Water → (R)-1-(4-(Trifluoromethyl)phenyl)-N-(6-(trifluoromethyl)pyridin-3-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide

HRID 445339Notes

Reaction equation

HRID 445339 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:35]=[N:36][C:37]([C:40]([F:43])([F:42])[F:41])=[CH:38][CH:39]=1.[H-].[Na+].O>CC#N>[F:31][C:2]([F:1])([F:32])[C:3]1[CH:4]=[CH:5][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]([NH:33][C:34]2[CH:35]=[N:36][C:37]([C:40]([F:43])([F:41])[F:42])=[CH:38][CH:39]=2)=[O:20])=[CH:7][CH:8]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 27377445-Amino-2-(trifluoromethyl)pyridineHCID 59536297(R)-4-Nitrophenyl 1-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate

Product 1

HCID 59536269(R)-1-(4-(Trifluoromethyl)phenyl)-N-(6-(trifluoromethyl)pyridin-3-yl)-3,4-dihydroisoquinoline-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 example 88) in MeCN (0.5 mL) was added 3-amino-6-(trifluoromethyl)pyridine (77 mg, 475 μmol). The resulting mixture was then subjected to a microwave irradiation at 150° C. for 15 min and at 180° C. for 15 min. Then, sodium hydride, 60% dispersion in mineral oil (18 mg, 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 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: 466 (M+H).

Workup

  1. customThe resulting mixture was then subjected to a microwave irradiation at 150° C. for 15 min and 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 purified by preparative HPLC (0%-100% MeCN 0.1% TFA/H2O 0.1% TFA)

Sources & evidence

ORD record
ord-cbedb6bcff1f4002957d9f083c8f7ade
Source dataset
uspto-grants-2013_07
Patent number
US08476297B2

Reaction notes

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