4-Fluorophenyl isocyanate → 8-fluoro-N-(4-fluorophenyl)-1-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-carboxamide

HRID 445252Notes

Reaction equation

HRID 445252 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[CH:10]([C:12]1[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][CH:13]=1)[NH:9][CH2:8][CH2:7]2.C(N(C(C)C)CC)(C)C.[F:31][C:32]1[CH:37]=[CH:36][C:35]([N:38]=[C:39]=[O:40])=[CH:34][CH:33]=1>ClCCCl.CO>[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[CH:10]([C:12]1[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:19])[F:20])=[CH:14][CH:13]=1)[N:9]([C:39]([NH:38][C:35]1[CH:36]=[CH:37][C:32]([F:31])=[CH:33][CH:34]=1)=[O:40])[CH2:8][CH2:7]2

Participants

6

Reactant 3

HCID 709554-Fluorophenyl isocyanateHCID 81531DiisopropylethylamineHCID 573263088-Fluoro-1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline

Product 1

HCID 426347328-fluoro-N-(4-fluorophenyl)-1-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-carboxamide

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 887MethanolSolvent

Procedure

A solution of 8-fluoro-1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline (0.4 g, 1.4 mmol) and diisopropylethylamine (0.5 mL, 2.9 mmol) in anhydrous 1,2-dichloroethane (10 mL) was treated with 4-fluorophenyl isocyanate (0.14 mL, 1.2 mmol) and stirred at RT for 16 h. The solvent was removed under vacuum and the residue was purified by preparative HPLC [gradient 10-90% MeCN (0.1% TFA)/H2O (0.1% TFA)] to give the pure product which was dissolved in methanol (10 mL) and neutralized by passing the solution through a Polymer Lab-HCO3 Macroporous resin cartridge, and the filtrate was concentrated to give 8-fluoro-N-(4-fluorophenyl)-1-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-carboxamide as a white solid. MS (ESI pos. ion) m/z: 433 (M+1).

Workup

  1. customThe solvent was removed under vacuum
  2. customthe residue was purified by preparative HPLC [gradient 10-90% MeCN (0.1% TFA)/H2O (0.1% TFA)]
  3. customto give the pure product which
  4. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-7cb19b6fcdad4ba1b41b06f56567f6d0
Source dataset
uspto-grants-2013_07
Patent number
US08476297B2

Reaction notes

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