Sodium hydride → 1-(5-Tert-butylisoxazol-3-yl)-3-(3-(7-methoxy-6-(3-(methylsulfonyl)propoxy)quinazolin-4-ylthio)phenyl)urea

HRID 871335ノート

反応式

HRID 871335 の反応式
[H-].[Na+].[C:3]([C:7]1[O:11][N:10]=[C:9]([NH:12][C:13]([NH:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([SH:22])[CH:17]=2)=[O:14])[CH:8]=1)([CH3:6])([CH3:5])[CH3:4].Cl[C:24]1[C:33]2[C:28](=[CH:29][C:30]([O:42][CH3:43])=[C:31]([O:34][CH2:35][CH2:36][CH2:37][S:38]([CH3:41])(=[O:40])=[O:39])[CH:32]=2)[N:27]=[CH:26][N:25]=1>O1CCCC1.C(OCC)(=O)C.O>[C:3]([C:7]1[O:11][N:10]=[C:9]([NH:12][C:13]([NH:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([S:22][C:24]3[C:33]4[C:28](=[CH:29][C:30]([O:42][CH3:43])=[C:31]([O:34][CH2:35][CH2:36][CH2:37][S:38]([CH3:41])(=[O:39])=[O:40])[CH:32]=4)[N:27]=[CH:26][N:25]=3)[CH:17]=2)=[O:14])[CH:8]=1)([CH3:6])([CH3:4])[CH3:5]

参加物

6

反応物 3

HCID 24758Sodium hydrideHCID 668758091-(5-Tert-butylisoxazol-3-yl)-3-(3-mercaptophenyl)ureaHCID 866535064-Chloro-7-methoxy-6-(3-(methylsulfonyl)propoxy)quinazoline

生成物 1

HCID 442168711-(5-Tert-butylisoxazol-3-yl)-3-(3-(7-methoxy-6-(3-(methylsulfonyl)propoxy)quinazolin-4-ylthio)phenyl)urea収率 4%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒2 回HCID 22728543Water ethylacetate溶媒

反応条件

温度
0 °C

実験手順

To a suspension of sodium hydride (11 mg, 0.44 mmol) in anhydrous tetrahydrofuran (2 mL) cooled to 0° C., was added 1-(5-tert-butylisoxazol-3-yl)-3-(3-mercaptophenyl)urea from the previous step (117 mg, 0.40 mmol) as a solution in tetrahydrofuran (1 mL) and the mixture stirred at 0° C. for 30 minutes. To this suspension 4-chloro-7-methoxy-6-(3-(methylsulfonyl)propoxy)quinazoline from Example 41B Step 1 (133 mg, 0.40 mmol) was added and the resulting mixture was stirred at 0° C. and slowly allowed to reach room temperature. After stirring for additional 1 h, the mixture was taken up in ethyl acetate/water and extracted. The combined organic layers were dried (MgSO4) and concentrated under reduced pressure. The residue was purified by preparative HPLC (Phenomenex phenylhexyl reverse phase column) to afford 1-(5-tert-butylisoxazol-3-yl)-3-(3-(7-methoxy-6-(3-(methylsulfonyl)propoxy)quinazolin-4-ylthio)phenyl)urea (10.30 mg, 4%) as a solid. 1H NMR (300 MHz, DMSO-d6) δ 9.73 (bs, 1H), 9.19 (bs, 1H), 8.70 (s, 1H), 7.85 (s, 1H), 7.53-7.27 (m, 5H), 6.49 (s, 1H), 4.32 (bs, 2H), 4.01 (s, 3H), 3.35 (2H), 3.07 (s, 3H), 2.28 (bs, 2H), 1.28 (s, 9H); LC-MS (ESI) m/z 586 (M+H)+.

後処理

  1. stirringthe resulting mixture was stirred at 0° C.
  2. customto reach room temperature
  3. stirringAfter stirring for additional 1 h
  4. extractionextracted
  5. dry with materialThe combined organic layers were dried (MgSO4)
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by preparative HPLC (Phenomenex phenylhexyl reverse phase column)

出典と根拠

ORDレコード
ord-c28bef6cab224166ac5fdd3f74ffec7a
出典データセット
uspto-grants-2015_03
特許番号
US08969587B2

反応ノート

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