2-Chloro-6,7-dimethoxyquinazoline → 4-[1-(6,7-Dimethoxyquinazolin-2-yl)piperidin-4-ylamino]benzoic acid tert-butyl ester

HRID 1274132ノート

反応式

HRID 1274132 の反応式
[C:1]([O:5][C:6](=[O:20])[C:7]1[CH:12]=[CH:11][C:10]([NH:13][CH:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)=[CH:9][CH:8]=1)([CH3:4])([CH3:3])[CH3:2].Cl[C:22]1[N:31]=[CH:30][C:29]2[C:24](=[CH:25][C:26]([O:34][CH3:35])=[C:27]([O:32][CH3:33])[CH:28]=2)[N:23]=1>C(O)CCCC>[C:1]([O:5][C:6](=[O:20])[C:7]1[CH:12]=[CH:11][C:10]([NH:13][CH:14]2[CH2:19][CH2:18][N:17]([C:22]3[N:31]=[CH:30][C:29]4[C:24](=[CH:25][C:26]([O:34][CH3:35])=[C:27]([O:32][CH3:33])[CH:28]=4)[N:23]=3)[CH2:16][CH2:15]2)=[CH:9][CH:8]=1)([CH3:4])([CH3:2])[CH3:3]

参加物

4

反応物 2

HCID 18181442-Chloro-6,7-dimethoxyquinazolineHCID 106362074-(Piperidin-4-ylamino)benzoic Acid tert-Butyl Ester

生成物 1

HCID 98256994-[1-(6,7-Dimethoxyquinazolin-2-yl)piperidin-4-ylamino]benzoic acid tert-butyl ester収率 20.8%

試薬・触媒・溶媒 1

HCID 62761-Pentanol溶媒

反応条件

温度
120 °C

実験手順

4-(Piperidin-4-ylamino)benzoic acid tert-butyl ester (49) (0.15 g, 0.54 mmol), was added to a solution of 2-chloro-6,7-dimethoxy-quinazoline (0.07 g, 0.31 mmol) in n-pentanol (5 mL) at 25° C. The mixture was stirred at 120° C. for 12 h. The reaction mixture was then cooled to room temperature and concentrated to a brown solid residue. Purification of the residue by flash column chromatography (gradient elution 30 to 40% EtOAc/hexanes) provided the title compound (0.03 g, 18%): TLC (Rf =0.50; 50% EtOAc/hexanes); 1H NMR (DMSO) δ 8.93 (s, 1H), 7.62 (d, 2H, J=8.7), 7.20 (s, 1H), 6.91 (s, 1H), 6.61 (d, 2H, J=8.8), 6.37 (d, 1H, J=7.9), 4.67 (d, 2H, J=13.2), 3.89 (s, 3H), 3.82 (s, 3H), 3.65 (m, 1H), 3.16 (t, 2H, J=11.5), 1.97 (d, 2H, J=10.4), 1.48 (s, 9H), 1.36 (m, 2H); 13C NMR (DMSO) δ 165.3, 158.6, 158.4, 156.1, 151.5, 149.3, 146.5, 130.9, 117.5, 113.9, 111.1, 105.4, 104.4, 78.9, 55.8, 55.6, 48.9, 42.5, 31.2, 28.0; HRMS (FAB) m/z 465.2503 (M+H)+ (C26H32N4O4 requires 465.2494); Anal. (C26H32N4O4 ·1/4HCl·1/4H2O) C, H, N.

後処理

  1. temperatureThe reaction mixture was then cooled to room temperature
  2. concentrationconcentrated to a brown solid residue
  3. customPurification of the residue
  4. washby flash column chromatography (gradient elution 30 to 40% EtOAc/hexanes)

出典と根拠

ORDレコード
ord-691e2fb4591c4957a196a98cc241bfa5
出典データセット
uspto-grants-2000_12
特許番号
US06156758

反応ノート

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