3-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline → HCID 58267858, compound

HRID 1918115Notes

Reaction equation

HRID 1918115 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].[F:23][C:24]([C:27]1[CH:31]=[C:30]([NH:32][C:33](=O)[O:34]C2C=CC=CC=2)[N:29]([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[N:28]=1)([F:26])[CH3:25]>C1COCC1.CN(C1C=CN=CC=1)C>[F:23][C:24]([C:27]1[CH:31]=[C:30]([NH:32][C:33]([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:34])[N:29]([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[N:28]=1)([F:26])[CH3:25]

Participants

5

Reactant 2

HCID 498410023-[(6,7-Dimethoxy-4-quinazolinyl)oxy]anilineHCID 66876696HCID 66876696, compound

Product 1

HCID 58267858HCID 58267858, compoundYield 62.2%

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-(1,1-difluoroethyl)-1-phenyl-1H-pyrazol-5-ylcarbamate (103 mg, 0.3 mmol), described in the previous step. The crude was purified by silica gel chromatography (DCM/MeOH 0-15%) and triturated in diethyl ether to afford 1-(3-(1,1-difluoroethyl)-1-phenyl-1H-pyrazol-5-yl)-3-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)urea (102 mg, 62%) as a solid. 1H NMR (300 MHz, DMSO-d6) δ 1.99 (t, J=18 Hz, 3H), 3.99 (s, 6H), 6.66 (s, 1H), 6.94 (d, J=9.6 Hz, 1H), 7.18 (d, J=9.6 Hz, 1H), 7.35-7.40 (m, 2H), 7.51-7.60 (m, 7H), 8.55 (s, 1H), 8.66 (s, 1H), 9.26 (s, 1H); LC-MS (ESI) m/z 547 (M+H)+.

Workup

  1. customprepared
  2. customThe crude was purified by silica gel chromatography (DCM/MeOH 0-15%)
  3. customtriturated in diethyl ether

Sources & evidence

ORD record
ord-aa710c2742af4621ba030cd3c1244806
Source dataset
uspto-grants-2013_12
Patent number
US08618289B2

Reaction notes

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