Water → 1-(3-cyclopropyl-1-phenyl-1H-pyrazol-5-yl)-3-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)urea

HRID 871758Notes

Reaction equation

HRID 871758 reaction equation
[CH:1]1([C:4]2[CH:8]=[C:7]([NH:9][C:10](=[O:18])OC3C=CC=CC=3)[N:6]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[N:5]=2)[CH2:3][CH2:2]1.[CH3:25][O:26][C:27]1[CH:28]=[C:29]2[C:34](=[CH:35][C:36]=1[O:37][CH3:38])[N:33]=[CH:32][N:31]=[C:30]2[O:39][C:40]1[CH:41]=[C:42]([CH:44]=[CH:45][CH:46]=1)[NH2:43].O>CS(C)=O>[CH:1]1([C:4]2[CH:8]=[C:7]([NH:9][C:10]([NH:43][C:42]3[CH:44]=[CH:45][CH:46]=[C:40]([O:39][C:30]4[C:29]5[C:34](=[CH:35][C:36]([O:37][CH3:38])=[C:27]([O:26][CH3:25])[CH:28]=5)[N:33]=[CH:32][N:31]=4)[CH:41]=3)=[O:18])[N:6]([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[N:5]=2)[CH2:2][CH2:3]1

Participants

5

Reactant 3

HCID 962WaterHCID 498410023-[(6,7-Dimethoxy-4-quinazolinyl)oxy]anilineHCID 66875916HCID 66875916, compound

Product 1

HCID 582678521-(3-cyclopropyl-1-phenyl-1H-pyrazol-5-yl)-3-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)ureaYield 33%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
70 °C

Procedure

A stirred mixture of phenyl 3-cyclopropyl-1-phenyl-1H-pyrazol-5-ylcarbamate (125 mg, 0.39 mmol) and 3-(6,7-dimethoxyquinazolin-4-yloxy)aniline (prepared as described in Example 113A) (100 mg, 0.34 mmol) in DMSO (1 mL) was heated to 70° C. for 18 h. After cooling to rt, water (20 mL) was added. The resulting suspension was filtered and the collected solid purified via preparative silica gel thin-layer chromatography (eluting with a mixture of 10:10:1 ethyl acetate:dichloromethane:methanol) to give a solid which was triturated with diethyl ether (50 mL) to afford 1-(3-cyclopropyl-1-phenyl-1H-pyrazol-5-yl)-3-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)urea (58 mg, 33%) as a colorless solid. 1H NMR (400 MHz, DMSO-d6) δ 9.21 (s, 1H), 8.55 (s, 1H), 8.49 (s, 1H), 7.51-7.55 (m, 6H), 7.34-7.39 (m, 3H), 7.17 (m, 1H), 6.91 (m, 1H), 6.14 (s, 1H), 3.99 (s, 3H), 3.98 (s, 3H), 1.86 (m, 1H), 0.86-0.88 (m, 2H), 0.65-0.67 (m, 2H); LC-MS (ESI) m/z 523 (M+H)+.

Workup

  1. temperatureAfter cooling to rt
  2. filtrationThe resulting suspension was filtered
  3. customthe collected solid purified via preparative silica gel thin-layer chromatography (
  4. washeluting with a mixture of 10:10:1 ethyl acetate
  5. customdichloromethane:methanol) to give a solid which
  6. customwas triturated with diethyl ether (50 mL)

Sources & evidence

ORD record
ord-cf95a0b4fc87444ea2033c588e0fb0c9
Source dataset
uspto-grants-2015_03
Patent number
US08969587B2

Reaction notes

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