Cesium carbonate → 1-(5-Tert-butylisoxazol-3-yl)-3-[3-(7-ethoxy-6-methoxyquinazolin-4-ylthio)phenyl]urea

HRID 631296노트

반응식

HRID 631296 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(C1ON=C(NC(NC2C=CC=C(O[C:41]3[C:50]4[C:45](=[CH:46][C:47]([O:53][CH2:54][CH3:55])=[C:48]([O:51][CH3:52])[CH:49]=4)[N:44]=[CH:43][N:42]=3)C=2)=O)C=1)(C)(C)C.C([O-])([O-])=O.[Cs+].[Cs+]>C(O)(C)C>[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:41]3[C:50]4[C:45](=[CH:46][C:47]([O:53][CH2:54][CH3:55])=[C:48]([O:51][CH3:52])[CH:49]=4)[N:44]=[CH:43][N:42]=3)[CH:15]=2)=[O:12])[CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

참가 물질

5

반응물 3

HCID 10796Cesium carbonateHCID 566583071-(5-Tert-butylisoxazol-3-yl)-3-[3-(7-ethoxy-6-methoxyquinazolin-4-yloxy)phenyl]ureaHCID 668758091-(5-Tert-butylisoxazol-3-yl)-3-(3-mercaptophenyl)urea

생성물 1

HCID 442433061-(5-Tert-butylisoxazol-3-yl)-3-[3-(7-ethoxy-6-methoxyquinazolin-4-ylthio)phenyl]urea수율 48%

시약·촉매·용매 1

HCID 3776Isopropanol용매

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온도
70 °C

실험 절차

A mixture of 1-(5-tert-butylisoxazol-3-yl)-3-(3-mercaptophenyl)urea described in Example 44A (0.146 g 0.5 mmol), 4-chloro-7-ethoxy-6-methoxyquinazoline from Example 6B Step 1 (0.12 g, 0.5 mmol), and Cs2CO3 (0.161 mg, 0.5 mmol) in isopropanol (10 mL) was heated at 70° C. for 7 hours. It was quenched with water and extracted with CH2Cl2. Extracts were dried over MgSO4 and concentrated under reduced pressure. It was purified by silica gel chromatography with EtOAc/hexane as eluant to afford 1-(5-tert-butylisoxazol-3-yl)-3-[3-(7-ethoxy-6-methoxyquinazolin-4-ylthio)phenyl]urea as solid (0.118 g, 48%). 1H NMR (300 MHz, CDCl3) δ 9.3 (br, 1H), 8.74 (s, 1H), 8.05 (s, 1H), 7.86 (s, 1H), 7.62 (d, 1H), 7.37 (m, 3H), 7.25 (1H), 5.91 (s, 1H), 4.29 (q, 2H), 4.06 (s, 3H), 1.58 (t, 3H), 1.32 (s, 9H); LC-MS (ESI) m/z 494 (M+H)+.

후처리

  1. customIt was quenched with water
  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 EtOAc/hexane as eluant

출처 및 근거

ORD 기록
ord-3c8b8c949f224048946fc4c9879b1281
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09320739B2

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