3-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline → 1-(3-(2-cyanopropan-2-yl)-1-phenyl-1H-pyrazol-5-yl)-3-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)urea

HRID 871693Notes

Reaction equation

HRID 871693 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[O:15][C:16]1[CH:17]=[C:18]([CH:20]=[CH:21][CH:22]=1)[NH2:19].[C:23]([C:25]([C:28]1[CH:32]=[C:31]([NH:33][C:34](=O)[O:35]C2C=CC=CC=2)[N:30]([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[N:29]=1)([CH3:27])[CH3:26])#[N:24]>C1COCC1.CN(C1C=CN=CC=1)C>[C:23]([C:25]([C:28]1[CH:32]=[C:31]([NH:33][C:34]([NH:19][C:18]2[CH:20]=[CH:21][CH:22]=[C:16]([O:15][C:6]3[C:5]4[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=4)[N:9]=[CH:8][N:7]=3)[CH:17]=2)=[O:35])[N:30]([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[N:29]=1)([CH3:27])[CH3:26])#[N:24]

Participants

5

Reactant 2

HCID 498410023-[(6,7-Dimethoxy-4-quinazolinyl)oxy]anilineHCID 67159368phenyl 3-(2-cyanopropan-2-yl)-1-phenyl-1H-pyrazol-5-ylcarbamate

Product 1

HCID 582679581-(3-(2-cyanopropan-2-yl)-1-phenyl-1H-pyrazol-5-yl)-3-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)ureaYield 47.1%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Using the procedure described in Example 306B, to a solution of 3-(6,7-dimethoxyquinazolin-4-yloxy)aniline (89 mg, 0.3 mmol), prepared as described in Example 113A, in THF (3.3 ml) was added DMAP (20 mg, 0.16 mmol) and phenyl 3-(2-cyanopropan-2-yl)-1-phenyl-1H-pyrazol-5-ylcarbamate (104 mg, 0.3 mmol) described in the previous step to afford 1-(3-(2-cyanopropan-2-yl)-1-phenyl-1H-pyrazol-5-yl)-3-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)urea (77.6 mg, 42%) as a solid. 1H NMR (300 MHz, DMSO-d6) δ 1.72 (s, 6H), 3.99 (s, 6H), 6.57 (s, 1H), 6.94 (d, J=6 Hz, 1H), 7.18 (d, J=6.6 Hz, 1H), 7.17-7.20 (m, 2H), 7.35-7.56 (m, 7H), 8.56 (s, 1H), 8.64 (s, 1H), 9.28 (s, 1H); LC-MS (ESI) m/z 550 (M+H)+.

Workup

  1. customprepared

Sources & evidence

ORD record
ord-7121dba6c53243a0b6b39d4c23d1d036
Source dataset
uspto-grants-2015_03
Patent number
US08969587B2

Reaction notes

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