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

HRID 1917747Notes

Reaction equation

HRID 1917747 reaction equation
[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]

Participants

5

Reactant 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

Product 1

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

Procedure

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)

Workup

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

Sources & evidence

ORD record
ord-7b2f426dcb664b6dabd928ae7550cdfd
Source dataset
uspto-grants-2013_12
Patent number
US08618289B2

Reaction notes

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