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

HRID 871340Notes

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].Cl[C:22]1[C:31]2[C:26](=[CH:27][C:28]([O:34][CH2:35][CH3:36])=[C:29]([O:32][CH3:33])[CH:30]=2)[N:25]=[CH:24][N:23]=1.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:22]3[C:31]4[C:26](=[CH:27][C:28]([O:34][CH2:35][CH3:36])=[C:29]([O:32][CH3:33])[CH:30]=4)[N:25]=[CH:24][N:23]=3)[CH:15]=2)=[O:12])[CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 70 °C

Procedure

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)+.

Workup

customIt was quenched with water
extractionextracted with CH2Cl2
dry with materialExtracts were dried over MgSO4
concentrationconcentrated under reduced pressure
customIt was purified by silica gel chromatography with EtOAc/hexane as eluant

Sources & evidence

ORD record: ord-b762455219cd4839b7e182e936f7c1a3
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08969587B2

Reaction notes

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