Phosgene → N-(3,4-dimethylbenzyl)-N'-(3-methyl-5-isoquinolinyl)urea

HRID 2056887

반응식

HRID 2056887 반응식
[CH3:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[CH3:10])[CH2:5][NH2:6].[C:11](Cl)(Cl)=[O:12].CCN(C(C)C)C(C)C.[NH2:24][C:25]1[CH:34]=[CH:33][CH:32]=[C:31]2[C:26]=1[CH:27]=[C:28]([CH3:35])[N:29]=[CH:30]2>C1(C)C=CC=CC=1>[CH3:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[CH3:10])[CH2:5][NH:6][C:11]([NH:24][C:25]1[CH:34]=[CH:33][CH:32]=[C:31]2[C:26]=1[CH:27]=[C:28]([CH3:35])[N:29]=[CH:30]2)=[O:12]

참가 물질

6

반응물 4

HCID 6371PhosgeneHCID 66888Benzenemethanamine, 3,4-dimethyl-HCID 81531DiisopropylethylamineHCID 122120553-Methylisoquinolin-5-amine

생성물 1

HCID 9996072N-(3,4-dimethylbenzyl)-N'-(3-methyl-5-isoquinolinyl)urea

시약·촉매·용매 1

HCID 1140Toluene용매2회

실험 절차

3,4-Dimethylbenzylamine (0.3 mL, 2.1 mmol) in toluene (11 mL) was added carefully to a 20% w/v solution of phosgene in toluene (4.5 mL). The mixture was refluxed overnight and was then concentrated in vacuo. The residue was then taken up in toluene (10 mL) and treated with DIEA (1.5 mL, 8.63 mmol) and 5-amino-3-methylisoquinoline (155 mg, 1.08 mmol). The reaction mixture was stirred at 80° for 2 h and was then cooled to room temperature. The precipitated solid was collected by filtration and was chromatographed on silica gel (97:3 CH2Cl2—CH3OH to 9:1 CH2Cl2—CH3OH, eluant gradient) to afford the desired product, A-473191. Treatment of this solid with methanolic HCl yielded the corresponding hydrochloride salt. 1H NMR (300 MHz, DMSO-d6) δ 9.16 (s, 1H), 8.59 (s, 1H), 8.24 (d, 1H, J=7.8 Hz), 7.74 (s, 1H), 7.68 (d, 1H, J=8.2 Hz), 7.50 (t, 1H, J=7.9 Hz), 7.08-7.12 (m, 3H), 6.95 (m, 1H), 4.28 (d, 2H, 5.8 Hz), 2.64 (s, 3H), 2.22 (s, 3H), 2.20 (s, 3H); MS (ESI30 ) m/z 320 (M+H).

후처리

  1. temperatureThe mixture was refluxed overnight
  2. concentrationwas then concentrated in vacuo
  3. filtrationThe precipitated solid was collected by filtration
  4. customwas chromatographed on silica gel (97:3 CH2Cl2—CH3OH to 9:1 CH2Cl2—CH3OH, eluant gradient)

출처 및 근거

ORD 기록
ord-460a3a5b640040d6907e5b3c246cb8ed
출처 데이터셋
uspto-grants-2008_02
특허 번호
US07335678B2

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