Diethyl Ether → 1-(3-(6,7-Dimethoxyquinazolin-4-ylthio)phenyl)-3-(3-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-5-yl)urea

HRID 871644Notes

Reaction equation

HRID 871644 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][N:7]=[C:6]2[S:15][C:16]1[CH:17]=[C:18]([CH:20]=[CH:21][CH:22]=1)[NH2:19].[F:23][C:24]([F:45])([F:44])[C:25]([C:28]1[CH:32]=[C:31]([NH:33][C:34](=O)[O:35]C2C=CC(Cl)=CC=2)[O:30][N:29]=1)([CH3:27])[CH3:26].C(OCC)C>C1COCC1.CN(C)C1C=CN=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][N:7]=[C:6]2[S:15][C:16]1[CH:17]=[C:18]([NH:19][C:34]([NH:33][C:31]2[O:30][N:29]=[C:28]([C:25]([CH3:27])([CH3:26])[C:24]([F:45])([F:44])[F:23])[CH:32]=2)=[O:35])[CH:20]=[CH:21][CH:22]=1

Participants

6

Reactant 3

HCID 3283Diethyl EtherHCID 569536273-(6,7-Dimethoxyquinazolin-4-ylthio)anilineHCID 569543124-Chlorophenyl 3-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-5-ylcarbamate

Product 1

HCID 442430451-(3-(6,7-Dimethoxyquinazolin-4-ylthio)phenyl)-3-(3-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-5-yl)ureaYield 69.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 3-(6,7-dimethoxyquinazolin-4-ylthio)aniline (76 mg, 0.24 mmol) described in Example 115B in anhydrous THF (1.5 mL), was added 4-chlorophenyl 3-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-5-ylcarbamate from Example 267A (84 mg, 0.24 mmol) and 4-(dimethylamino)pyridine (15 mg, 0.12 mmol). The mixture was stirred at rt for 6 h. To the suspension was added diethyl ether. Sonication and filtration afforded 1-(3-(6,7-dimethoxyquinazolin-4-ylthio)phenyl)-3-(3-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-5-yl)urea (88.8 mg, 69%) as a colorless solid. 1H NMR (300 MHz, DMSO-d6) δ 10.48 (s, 1H), 9.17 (s, 1H), 8.69 (s, 1H), 7.85 (s, 1H), 7.56 (d, J=9 Hz, 1H), 7.43-7.48 (m, 1H), 7.30-7.36 (m, 3H), 6.19 (s, 1H), 3.99 (s, 6H), 1.49 (s, 6H); LC-MS (ESI) m/z 534 (M+H)+.

Workup

  1. customSonication and filtration

Sources & evidence

ORD record
ord-1e9792def3f0457d938502e401805238
Source dataset
uspto-grants-2015_03
Patent number
US08969587B2

Reaction notes

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