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Tetrahydrofuran → 1-(5-Tert-butylisoxazol-3-yl)-3-(3-(6-ethoxy-7-methoxyquinazolin-4-ylthio)phenyl)urea

HRID 631305
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HRID 631305 반응식
[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:21](=[O:24])([O-])[O-].[Cs+].[Cs+].C(C1ON=[C:33]([NH:36][C:37]([NH:39][C:40]2[CH:45]=[CH:44][C:43](Cl)=[C:42](O)[CH:41]=2)=O)C=1)(C)(C)C.C1C[O:51][CH2:50][CH2:49]1>>[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:33]3[C:41]4[C:40](=[CH:45][C:44]([O:24][CH3:21])=[C:43]([O:51][CH2:50][CH3:49])[CH:42]=4)[N:39]=[CH:37][N:36]=3)[CH:15]=2)=[O:12])[CH:6]=1)([CH3:4])([CH3:2])[CH3:3]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

5

반응물 4

HCID 8028TetrahydrofuranHCID 10796Cesium carbonateHCID 668758091-(5-Tert-butylisoxazol-3-yl)-3-(3-mercaptophenyl)ureaHCID 668773621-(5-Tert-butylisoxazol-3-yl)-3-(4-chloro-3-hydroxyphenyl)urea

생성물 1

HCID 582677211-(5-Tert-butylisoxazol-3-yl)-3-(3-(6-ethoxy-7-methoxyquinazolin-4-ylthio)phenyl)urea수율 66.5%

실험 절차

In a sealed reaction vessel 1-(5-tert-butylisoxazol-3-yl)-3-(3-mercaptophenyl)urea described in Example 44A (333 mg, 1.14 mmol) was dissolved in 11 mL of THF. To this solution was added cesium carbonate (447 mg, 1.37 mmol), and the solution stirred for 30 minutes. At the end of this time 4-chloro-6-ethoxy-7-methoxyquinazoline (273 mg, 1.14 mmol) from Example 10A and the reaction heated to 50° C. for 48 hours. The reaction was concentrated and purified by silica gel chromatography eluting with an ethyl acetate/dichloromethane gradient 0-50% over 75 minutes. Concentration of the main peak gave the title compound (374 mg, 66.5% yield). 1H NMR (300 MHz, DMSO-d6) δ 9.58 (s, 1H), 9.01 (s, 1H), 8.69 (s, 1H), 7.48 (s, 1H), 7.55-7.25 (m, 5H), 6.49 (s, 1H), 4.25 (m, 2H), 3.99 (s, 3H), 1.47 (m, 3H), 1.32 (s, 9H). LCMS (ESI) m/z 494 (M+H)

후처리

  1. concentrationThe reaction was concentrated
  2. custompurified by silica gel chromatography
  3. washeluting with an ethyl acetate/dichloromethane gradient 0-50% over 75 minutes

출처 및 근거

ORD 기록
ord-12753fe50f704d3a856d9e1ad5218bc3
출처 데이터셋
uspto-grants-2016_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09320739B2

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