Phosphorus oxychloride → Methyl 4-{[4-chloro-3-(trifluoromethyl)benzyl]amino}-6-nitroquinazoline-8-carboxylate

HRID 578642ノート

反応式

HRID 578642 の反応式
[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[C:12]([C:14]([O:16][CH3:17])=[O:15])[CH:13]=1)[N:10]=[CH:9][NH:8][C:7]2=O)([O-:3])=[O:2].O=P(Cl)(Cl)Cl.CCN(C(C)C)C(C)C.[Cl:33][C:34]1[CH:41]=[CH:40][C:37]([CH2:38][NH2:39])=[CH:36][C:35]=1[C:42]([F:45])([F:44])[F:43]>ClCCCl>[Cl:33][C:34]1[CH:41]=[CH:40][C:37]([CH2:38][NH:39][C:7]2[C:6]3[C:11](=[C:12]([C:14]([O:16][CH3:17])=[O:15])[CH:13]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:10]=[CH:9][N:8]=2)=[CH:36][C:35]=1[C:42]([F:43])([F:44])[F:45]

参加物

6

反応物 4

HCID 24813Phosphorus oxychlorideHCID 81531DiisopropylethylamineHCID 485440Benzenemethanamine, 4-chloro-3-(trifluoromethyl)-HCID 136278294Methyl 6-nitro-4-oxo-3,4-dihydroquinazoline-8-carboxylate

生成物 1

HCID 66763565Methyl 4-{[4-chloro-3-(trifluoromethyl)benzyl]amino}-6-nitroquinazoline-8-carboxylate収率 46%

試薬・触媒・溶媒 1

HCID 111,2-Dichloroethane溶媒

反応条件

温度
90 °C

実験手順

To a solution of methyl 6-nitro-4-oxo-3,4-dihydroquinazoline-8-carboxylate (250 mg, 1.0 mmol) in 5 mL of anhydrous DCE, POCl3 (110 μL, 1.2 mmol, 1.2 equiv.) was added followed by DIPEA (870 μL, 5.0 mmol, 5.0 equiv.). The resulting mixture was stirred at 90° C. for 1 h. After cooling down to rt, 4-chloro-3-(trifluoromethyl)benzylamine (230 mg, 1.1 mmol, 1.1 equiv.) was added. The reaction mixture was stirred at 80° C. for 3 h. After work-up, the crude was purified by flash chromatography to yield the title compound in 46% yield. 1HNMR (in DMSO): 3.91 (s, 3H), 4.88 (d, J=5.9 Hz, 2H), 7.65-7.71 (m, 2H), 7.91 (s, 1H), 8.64 (s 1H), 8.68 (d, J=2.2 Hz, 1H), 9.49 (d, J=2.4 Hz, 1H), 9.70 (t, J=5.7 Hz, 1H). Mass: M+H+: 441.

後処理

  1. temperatureAfter cooling down to rt
  2. stirringThe reaction mixture was stirred at 80° C. for 3 h
  3. customAfter work-up, the crude was purified by flash chromatography

出典と根拠

ORDレコード
ord-1df950d5d7bb41a1a832ed26a83794cd
出典データセット
uspto-grants-2015_05
特許番号
US09040560B2

反応ノート

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