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

HRID 586000

反応式

HRID 586000 の反応式
[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]

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒2 回

実験手順

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 (ESI+) m/z 320 (M+H).

後処理

  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)

出典と根拠

ORDレコード
ord-f6b5a55bb2814050820a8d2b82986a16
出典データセット
uspto-grants-2005_08
特許番号
US06933311B2

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