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

HRID 887280노트

반응식

HRID 887280 반응식
[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]

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 1140Toluene용매2회

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-d91f034430704044967cb148c5eb9ae9
출처 데이터셋
uspto-grants-2012_08
특허 번호
US08247413B2

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