3-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline → HCID 56954225, compound

HRID 1918091Notes

Reaction equation

HRID 1918091 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]1([N:29]2[C:33]([NH:34][C:35](=O)[O:36]C3C=CC=CC=3)=[CH:32][C:31]([C:44]([CH3:50])([CH3:49])[C:45]([F:48])([F:47])[F:46])=[N:30]2)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>C1COCC1.CN(C1C=CN=CC=1)C>[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]([NH:19][C:35]([NH:34][C:33]2[N:29]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[N:30]=[C:31]([C:44]([CH3:50])([CH3:49])[C:45]([F:48])([F:47])[F:46])[CH:32]=2)=[O:36])[CH:20]=[CH:21][CH:22]=1

Participants

5

Reactant 2

HCID 498410023-[(6,7-Dimethoxy-4-quinazolinyl)oxy]anilineHCID 56954419HCID 56954419, compound

Product 1

HCID 56954225HCID 56954225, compoundYield 62%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

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 1-phenyl-3-(1,1,1-trifluoro-2-methylpropan-2-yl)-1H-pyrazol-5-ylcarbamate (104 mg, 0.3 mmol) described in the previous step. The reaction mixture was stirred at rt overnight, then concentrated under reduced pressure. The crude was purified by silica gel chromatography (hexane/ethyl acetate 25-100%) and triturated in diethyl ether to afford 1-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-(1-phenyl-3-(1,1,1-trifluoro-2-methylpropan-2-yl)-1H-pyrazol-5-yl)urea (103 mg, 62%) as a solid. 1H NMR (300 MHz, DMSO-d6) δ 1.56 (s, 6H), 4.02 (s, 6H), 6.55 (s, 1H), 6.94 (d, J=9 Hz, 1H), 7.17 (d, J=9 Hz, 1H), 7.34-7.57 (m, 9H), 8.55-8.59 (m, 2H), 9.28 (s, 1H); LC-MS (ESI) m/z 593 (M+H)+.

Workup

  1. concentrationconcentrated under reduced pressure
  2. customThe crude was purified by silica gel chromatography (hexane/ethyl acetate 25-100%)
  3. customtriturated in diethyl ether

Sources & evidence

ORD record
ord-a77d395e518948018476b62776049f58
Source dataset
uspto-grants-2013_12
Patent number
US08618289B2

Reaction notes

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