4-Fluorophenyl isocyanate → HCID 57326211, compound

HRID 445294Notes

Reaction equation

HRID 445294 reaction equation
[F:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][NH:6][CH:7]2[C:12]1[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][CH:13]=1.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>ClCCl.CO>[F:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6]([C:39]([NH:38][C:35]1[CH:36]=[CH:37][C:32]([F:31])=[CH:33][CH:34]=1)=[O:40])[CH:7]2[C:12]1[CH:17]=[CH:16][C:15]([C:18]([F:19])([F:20])[F:21])=[CH:14][CH:13]=1

Participants

6

Reactant 3

HCID 709554-Fluorophenyl isocyanateHCID 81531DiisopropylethylamineHCID 59536259HCID 59536259, compound

Product 1

HCID 57326211HCID 57326211, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 5-fluoro-1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline (0.27 g, 0.897 mmol) and diisopropylethylamine (0.2 mL, 0.919 mmol) in anhydrous dichloromethane (6 mL) was treated with 4-fluorophenyl isocyanate (0.105 mL, 0.934 mmol) and stirred at RT for 16 h. The solvent was removed in vacuo 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 5-fluoro-N-(4-fluorophenyl)-1-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-carboxamide as a colorless oil. MS (ESI pos. ion) m/z: 433 (M+H).

Workup

  1. customThe solvent was removed in vacuo
  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-a8b9a1c780a548e6b46f7d9fb6f569fe
Source dataset
uspto-grants-2013_07
Patent number
US08476297B2

Reaction notes

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