Diisopropylethylamine → US9730937, Example 159

HRID 631467ノート

反応式

HRID 631467 の反応式
[F:1][CH2:2][C:3]([C:7]1[CH:11]=[C:10]([NH:12][C:13](=[O:21])OC2C=CC=CC=2)[O:9][N:8]=1)([CH3:6])[CH2:4][F:5].[CH3:22][O:23][C:24]1[CH:25]=[C:26]2[C:31](=[CH:32][C:33]=1[O:34][CH3:35])[N:30]=[CH:29][N:28]=[C:27]2[O:36][C:37]1[CH:38]=[C:39]([CH:41]=[CH:42][CH:43]=1)[NH2:40].C(N(CC)C(C)C)(C)C>C1COCC1>[F:5][CH2:4][C:3]([C:7]1[CH:11]=[C:10]([NH:12][C:13]([NH:40][C:39]2[CH:41]=[CH:42][CH:43]=[C:37]([O:36][C:27]3[C:26]4[C:31](=[CH:32][C:33]([O:34][CH3:35])=[C:24]([O:23][CH3:22])[CH:25]=4)[N:30]=[CH:29][N:28]=3)[CH:38]=2)=[O:21])[O:9][N:8]=1)([CH3:6])[CH2:2][F:1]

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 498410023-[(6,7-Dimethoxy-4-quinazolinyl)oxy]anilineHCID 66876760Phenyl 3-(1,3-difluoro-2-methylpropan-2-yl)isoxazol-5-ylcarbamate

生成物 1

HCID 56953993US9730937, Example 159収率 58%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
50 °C

実験手順

A mixture of phenyl 3-(1,3-difluoro-2-methylpropan-2-yl)isoxazol-5-ylcarbamate (0.158 g, 0.5 mmol), 3-(6,7-dimethoxyquinazolin-4-yloxy)aniline from Example 113A (0.119 g, 0.4 mmol), and N,N-diisopropylethylamine (0.8 mL) in THF (6 mL) was heated at 50° C. for 5 hours. It was quenched with saturated NaHCO3 and extracted with CH2Cl2. Extracts were dried over MgSO4 and concentrated under reduced pressure. It was purified by silica gel chromatography with 40-95% EtOAc/hexane as eluants to afford 1-[3-(1,3-difluoro-2-methylpropan-2-yl)isoxazol-5-yl]-3-[3-(6,7-dimethoxyquinazolin-4-yloxy]phenyl)urea as solid (0.115 g, 58%). 1H NMR (300 MHz, DMSO-d6) δ 10.33 (s, 1H), 9.00 (s, 1H), 8.55 (s, 1H), 7.56 (m, 3H), 7.39 (s, 1H), 7.27 (s and d, 2H), 6.24 (s, 1H), 4.73 (m, 2H), 4.56 (m, 2H), 3.99 (s, 3H), 3.98 (s, 3H), 1.30 (s, 3H); LC-MS (ESI) m/z 500 (M+H)+.

後処理

  1. customIt was quenched with saturated NaHCO3
  2. extractionextracted with CH2Cl2
  3. dry with materialExtracts were dried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customIt was purified by silica gel chromatography with 40-95% EtOAc/hexane as eluants

出典と根拠

ORDレコード
ord-231ef16bbc2a40b985ad36d7980dbb16
出典データセット
uspto-grants-2016_04
特許番号
US09320739B2

反応ノート

読み込み中…