Phosgene → N-[4-fluoro-3-(trifluoromethyl)benzyl]-N'-(3-methyl-5-isoquinolinyl)urea

HRID 2056899Notes

Reaction equation

HRID 2056899 reaction equation
[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][NH2:7])=[CH:4][C:3]=1[C:10]([F:13])([F:12])[F:11].[C:14](Cl)(Cl)=[O:15].CCN(C(C)C)C(C)C.[NH2:27][C:28]1[CH:37]=[CH:36][CH:35]=[C:34]2[C:29]=1[CH:30]=[C:31]([CH3:38])[N:32]=[CH:33]2>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][NH:7][C:14]([NH:27][C:28]2[CH:37]=[CH:36][CH:35]=[C:34]3[C:29]=2[CH:30]=[C:31]([CH3:38])[N:32]=[CH:33]3)=[O:15])=[CH:4][C:3]=1[C:10]([F:11])([F:12])[F:13]

Participants

6

Reactant 4

HCID 6371PhosgeneHCID 81531DiisopropylethylamineHCID 522270[4-Fluoro-3-(trifluoromethyl)phenyl]methanamineHCID 122120553-Methylisoquinolin-5-amine

Product 1

HCID 22032629N-[4-fluoro-3-(trifluoromethyl)benzyl]-N'-(3-methyl-5-isoquinolinyl)urea

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

4-Fluoro-3-(trifluoromethyl)benzylamine (0.8 g, 4.15 mmol) in toluene (20 mL) was refluxed with 20% w/v phosgene solution in toluene (2.1 mL) overnight. The mixture was cooled to room temperature and concentrated in vacuo. The residue was again taken up in toluene (25 mL) and was stirred overnight at 80° C. with DIEA (2 mL, 11.5 mmol) and 5-amino-3-methylisoquinoline (500 mg, 3.16 mmol). The mixture was cooled to room temperature, concentrated in vacuo, and the residue was purified by silica gel chromatography (97:3 CH2Cl2:CH3OH, eluant) to provide the title compound. The corresponding hydrochloride salt was prepared by treatment with methanolic HCl. 1H NMR (300 MHz, DMSO-d6) δ 9.18 (s, 1H), 8.72 (s, 1H), 8.16 (d, 1H, J=7.8 Hz), 7.70-7.77 (m, 4H), 7.48-7.54 (m, 3H), 7.14 (t, 1H, J=5.9 Hz), 4.42 (d, 2H, J=6.1 Hz), 2.64 (s, 3H); MS (ESI+) m/z 378 (M+H).

Workup

  1. concentrationconcentrated in vacuo
  2. temperatureThe mixture was cooled to room temperature
  3. concentrationconcentrated in vacuo
  4. customthe residue was purified by silica gel chromatography (97:3 CH2Cl2:CH3OH, eluant)

Sources & evidence

ORD record
ord-e9f2bc0a32994b269096f5ac35acd319
Source dataset
uspto-grants-2008_02
Patent number
US07335678B2

Reaction notes

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