Cesium carbonate → 1-(5-Tert-butylisoxazol-3-yl)-3-[3-(6,7-diethoxyquinazolin-4-yloxy)phenyl]urea

HRID 631220Notes

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]([OH: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:35][CH2:36][CH3:37])=[C:29]([O:32][CH2:33][CH3:34])[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]([O:20][C:22]3[C:31]4[C:26](=[CH:27][C:28]([O:35][CH2:36][CH3:37])=[C:29]([O:32][CH2:33][CH3:34])[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: 90 °C

Procedure

A mixture of 1-(5-tert-butylisoxazol-3-yl)-3-(3-hydroxyphenyl)urea from Example 1A (0.137 g, 0.5 mmol), 4-chloro-6,7-diethoxyquinazoline from the previous step (0.126 g, 0.5 mmol), and Cs2CO3 (0.326 g, 1 mmol) in isopropanol (6 mL) was heated at 90° C. for 4 hours. The reaction was quenched with water and extracted with CH2Cl2. Extracts were dried over MgSO4 and concentrated under reduced pressure. The residue was purified by silica gel chromatography with EtOAc/hexane as eluant to afford 1-(5-tert-butylisoxazol-3-yl)-3-[3-(6,7-diethoxyquinazolin-4-yloxy)phenyl]urea as a solid. 1H NMR (300 MHz, DMSO-d6) δ 9.59 (s, 1H), 9.03 (s, 1H), 8.56 (s, 1H), 7.57 (m, 1H), 7.55 (s, 1H), 7.40 (t, 1H), 7.37 (s, 1H), 7.25 (d, 1H), 6.96 (dd, 1H), 6.47 (s, 1H), 4.26 (m 4H), 1.43 (m, 6H), 1.27 (s, 9H).

Workup

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

Sources & evidence

ORD record: ord-397e658ee6db43e98387a92524bb4959
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09320739B2

Reaction notes

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