Cesium carbonate → 1-(3-(7-(Benzyloxy)quinazolin-4-yloxy)phenyl)-3-(5-tert-butylisoxazol-3-yl)urea

HRID 631289Notes

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].[CH2:21]([O:28][C:29]1[CH:38]=[C:37]2[C:32]([C:33](Cl)=[N:34][CH:35]=[N:36]2)=[CH:31][CH:30]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCCC1>[CH2:21]([O:28][C:29]1[CH:38]=[C:37]2[C:32]([C:33]([O:20][C:16]3[CH:15]=[C:14]([NH:13][C:11]([NH:10][C:7]4[CH:6]=[C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])[O:9][N:8]=4)=[O:12])[CH:19]=[CH:18][CH:17]=3)=[N:34][CH:35]=[N:36]2)=[CH:31][CH:30]=1)[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

Participants

Conditions

Temperature: 50 °C

Procedure

Following to the procedure described in Example 41C, 1-(5-tert-butylisoxazol-3-yl)-3-(3-hydroxyphenyl)urea (1.02 g, 3.7 mmol) from Example 1A was reacted with 7-(benzyloxy)-4-chloroquinazoline (1 g, 3.7 mmol) and cesium carbonate (24 g, 7.4 mmol) in anhydrous tetrahydrofuran (10 mL) and the mixture was heated at 50° C. overnight. The crude product was triturated with dichloromethane to give 1-(3-(7-(benzyloxy)quinazolin-4-yloxy)phenyl)-3-(5-tert-butylisoxazol-3-yl)urea (725 mg, 38%) as a solid. 1H NMR (300 MHz, DMSO-d6) δ 9.59 (s, 1H), 9.01 (s, 1H), 8.65 (s, 1H), 8.29 (d, 1H), 7.57-7.38 (m, 9H), 7.28 (d, 1H), 6.98 (d, 1H), 6.48 (s, 1H), 5.37 (s, 2H), 1.27 (s, 9H); LC-MS (ESI) m/z 510 (M+H)+.

Workup

customThe crude product was triturated with dichloromethane

Sources & evidence

ORD record: ord-7b30492027b84235a5190726c38a6de7
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09320739B2

Reaction notes

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