1-(3-(6,7-Dimethoxyquinazolin-4-yloxy)phenyl)-3-(3-isopropylisoxazol-5-yl)urea → 1-(3-Cyclopropylisoxazol-5-yl)-3-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)urea

HRID 1917852Notes

Reaction equation

HRID 1917852 reaction equation
COC1C=C2C(=CC=1OC)N=CN=C2OC1C=C(C=CC=1)N.C1(C2C=C(NC(=O)OC3C=CC=CC=3)ON=2)CC1.[CH3:41][O:42][C:43]1[CH:44]=[C:45]2[C:50](=[CH:51][C:52]=1[O:53][CH3:54])[N:49]=[CH:48][N:47]=[C:46]2[O:55][C:56]1[CH:57]=[C:58]([NH:62][C:63]([NH:65][C:66]2[O:70][N:69]=[C:68]([CH:71]([CH3:73])[CH3:72])[CH:67]=2)=[O:64])[CH:59]=[CH:60][CH:61]=1>>[CH:71]1([C:68]2[CH:67]=[C:66]([NH:65][C:63]([NH:62][C:58]3[CH:59]=[CH:60][CH:61]=[C:56]([O:55][C:46]4[C:45]5[C:50](=[CH:51][C:52]([O:53][CH3:54])=[C:43]([O:42][CH3:41])[CH:44]=5)[N:49]=[CH:48][N:47]=4)[CH:57]=3)=[O:64])[O:70][N:69]=2)[CH2:73][CH2:72]1

Participants

4

Reactant 3

HCID 442434351-(3-(6,7-Dimethoxyquinazolin-4-yloxy)phenyl)-3-(3-isopropylisoxazol-5-yl)ureaHCID 498410023-[(6,7-Dimethoxy-4-quinazolinyl)oxy]anilineHCID 59394778Phenyl 3-cyclopropylisoxazol-5-ylcarbamate

Product 1

HCID 442434371-(3-Cyclopropylisoxazol-5-yl)-3-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)ureaYield 49%

Procedure

3-(6,7-dimethoxyquinazolin-4-yloxy)aniline from Example 113A (89 mg, 0.3 mmol) and phenyl 3-cyclopropylisoxazol-5-ylcarbamate from the previous step (88 mg, 0.36 mmol) were reacted according to the method described for 1-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-(3-isopropylisoxazol-5-yl)urea in Example 122B to afford 1-(3-cyclopropylisoxazol-5-yl)-3-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)urea as a colorless solid (65 mg, 49%). 1H NMR (300 MHz, DMSO-d6) δ 10.17 (brs, 1H), 9.05 (brs, 1H), 8.56 (s, 1H), 7.56 (s, 2H), 7.38-7.44 (m, 2H), 7.29 (m, 1H), 6.99 (m, 1H), 5.77 (s, 1H), 3.98-4.00 (2×s, 6H), 1.91 (m, 1H), 0.94-0.99 (m, 2H), 0.71-0.75 (m, 2H); LC-MS (ESI) m/z 448 (M+H)+.

Sources & evidence

ORD record
ord-bfdb5cb63c3748b9a7114b45c345560c
Source dataset
uspto-grants-2013_12
Patent number
US08618289B2

Reaction notes

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