Diisopropylethylamine → 1-(3-(6-Methoxy-7-(2-methoxyethoxy)quinazolin-4-yloxy)phenyl)-3-(5-phenylisoxazol-3-yl)urea

HRID 1917972ノート

反応式

HRID 1917972 の反応式
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][O:16][CH3:17])[N:9]=[CH:8][N:7]=[C:6]2[O:18][C:19]1[CH:20]=[C:21]([CH:23]=[CH:24][CH:25]=1)[NH2:22].C(N(CC)C(C)C)(C)C.[C:35]1([C:41]2[O:45][N:44]=[C:43]([NH:46][C:47](=O)[O:48]C3C=CC=CC=3)[CH:42]=2)[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>C1COCC1.CN(C)C1C=CN=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][O:16][CH3:17])[N:9]=[CH:8][N:7]=[C:6]2[O:18][C:19]1[CH:20]=[C:21]([NH:22][C:47]([NH:46][C:43]2[CH:42]=[C:41]([C:35]3[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=3)[O:45][N:44]=2)=[O:48])[CH:23]=[CH:24][CH:25]=1

参加物

6

反応物 3

HCID 81531DiisopropylethylamineHCID 59394374Phenyl 5-phenylisoxazol-3-ylcarbamateHCID 668758053-(6-Methoxy-7-(2-methoxyethoxy)quinazolin-4-yloxy)aniline

生成物 1

HCID 582679091-(3-(6-Methoxy-7-(2-methoxyethoxy)quinazolin-4-yloxy)phenyl)-3-(5-phenylisoxazol-3-yl)urea収率 70%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
50 °C

実験手順

According to the procedure described in Example 113C, 3-(6-methoxy-7-(2-methoxyethoxy)quinazolin-4-yloxy)aniline from Example 117B (102 mg, 0.3 mmol) in THF (1.5 mL) was treated with N,N-diisopropylethylamine (68 μl, 0.39 mmol), 4-(dimethylamino)pyridine (1.8 mg, 0.015 mmol) and phenyl 5-phenylisoxazol-3-ylcarbamate from Example 113B (109 mg, 0.39 mmol). The reaction mixture was heated to 50° C. for 4 h. After cooling to room temperature, the mixture was partitioned between chloroform and a saturated solution of sodium bicarbonate. The water phase was back extracted three times with chloroform and the organics combined and dried (MgSO4). Concentration under reduced pressure gave a residue which was purified by preparative HPLC (phenylhexyl reverse phase column). The obtained solid was triturated with anhydrous diethyl ether to afford 1-(3-(6-methoxy-7-(2-methoxyethoxy)quinazolin-4-yloxy)phenyl)-3-(5-phenylisoxazol-3-yl)urea as a white solid (110 mg, 70%). 1H NMR (300 MHz, DMSO-d6) δ 9.74 (s, 1H), 9.06 (s, 1H), 8.57 (s, 1H), 7.86 (d, 2H), 7.62-7.53 (m, 5H), 7.51 (t, 2H), 7.28 (m, 2H), 6.99 (d, 1H), 4.34 (bs, 2H), 4.00 (s, 3H), 3.77 (bs, 2H), 3.35 (s, 3H); LC-MS (ESI) m/z 528 (M+H)+.

後処理

  1. temperatureAfter cooling to room temperature
  2. customthe mixture was partitioned between chloroform
  3. extractionThe water phase was back extracted three times with chloroform
  4. dry with materialdried (MgSO4)
  5. concentrationConcentration under reduced pressure
  6. customgave a residue which
  7. customwas purified by preparative HPLC (phenylhexyl reverse phase column)
  8. customThe obtained solid was triturated with anhydrous diethyl ether

出典と根拠

ORDレコード
ord-28b306467a3a43e69169c4fa98ca5a9f
出典データセット
uspto-grants-2013_12
特許番号
US08618289B2

反応ノート

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