Cesium carbonate → 1-(5-Tert-butylisoxazol-3-yl)-3-(3-(7-methoxy-6-(2-methoxyethoxy)quinazolin-4-ylthio)phenyl)urea

HRID 871336ノート

反応式

HRID 871336 の反応式
[C:1]([C:5]1[O:9][N:8]=[C:7]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([SH:20])[CH:15]=2)=[O:12])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].Cl[C:28]1[C:37]2[C:32](=[CH:33][C:34]([O:43][CH3:44])=[C:35]([O:38][CH2:39][CH2:40][O:41][CH3:42])[CH:36]=2)[N:31]=[CH:30][N:29]=1>O1CCCC1>[C:1]([C:5]1[O:9][N:8]=[C:7]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([S:20][C:28]3[C:37]4[C:32](=[CH:33][C:34]([O:43][CH3:44])=[C:35]([O:38][CH2:39][CH2:40][O:41][CH3:42])[CH:36]=4)[N:31]=[CH:30][N:29]=3)[CH:15]=2)=[O:12])[CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

参加物

5

反応物 3

HCID 10796Cesium carbonateHCID 109344884-Chloro-7-methoxy-6-(2-methoxyethoxy)quinazolineHCID 668758091-(5-Tert-butylisoxazol-3-yl)-3-(3-mercaptophenyl)urea

生成物 1

HCID 582679221-(5-Tert-butylisoxazol-3-yl)-3-(3-(7-methoxy-6-(2-methoxyethoxy)quinazolin-4-ylthio)phenyl)urea収率 50%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

1-(5-tert-butylisoxazol-3-yl)-3-(3-mercaptophenyl)urea described in Example 44A (223 mg, 0.83 mmol) was treated with cesium carbonate (325 mg, 1.0 mmol) in anhydrous tetrahydrofuran (8 mL). The mixture was stirred at room temperature for 30 minutes. 4-chloro-7-methoxy-6-(2-methoxyethoxy)quinazoline (149 mg, 0.45 mmol) from Example 15A was added to the suspension and the mixture heated to 50° C. overnight. After cooling to room temperature the mixture was concentrated under reduced pressure and the residue purified by silica gel chromatography (ethyl acetate/dichloromethane 1:1) to give 1-(5-tert-butylisoxazol-3-yl)-3-(3-(7-methoxy-6-(2-methoxyethoxy)quinazolin-4-ylthio)phenyl)urea (218 mg, 50%) as a solid. 1H NMR (300 MHz, DMSO-d6) δ 9.58 (s, 1H), 9.00 (s, 1H), 8.69 (s, 1H), 7.85 (s, 1H), 7.52-7.27 (m, 5H), 6.49 (s, 1H), 4.32 (bs, 2H), 4.00 (s, 3H), 3.77 (bs, 2H), 3.36 (s, 3H), 1.27 (s, 9H); LC-MS (ESI) m/z 524 (M+H)+.

後処理

  1. temperaturethe mixture heated to 50° C. overnight
  2. temperatureAfter cooling to room temperature the mixture
  3. concentrationwas concentrated under reduced pressure
  4. customthe residue purified by silica gel chromatography (ethyl acetate/dichloromethane 1:1)

出典と根拠

ORDレコード
ord-f100f4230b4443b4817d8c434d7770aa
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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