Diisopropylethylamine → 1-[3-(1,3-difluoro-2-methylpropan-2-yl)-1-phenyl-1H-pyrazol-5-yl]-3-[3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl]urea

HRID 631492Notes

Reaction equation

HRID 631492 reaction equation
[F:1][CH2:2][C:3]([C:7]1[CH:11]=[C:10]([NH:12][C:13](=[O:21])OC2C=CC=CC=2)[N:9]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[N:8]=1)([CH3:6])[CH2:4][F:5].[CH3:28][O:29][C:30]1[CH:31]=[C:32]2[C:37](=[CH:38][C:39]=1[O:40][CH3:41])[N:36]=[CH:35][N:34]=[C:33]2[O:42][C:43]1[CH:44]=[C:45]([CH:47]=[CH:48][CH:49]=1)[NH2:46].C(N(CC)C(C)C)(C)C>C1COCC1>[F:1][CH2:2][C:3]([C:7]1[CH:11]=[C:10]([NH:12][C:13]([NH:46][C:45]2[CH:47]=[CH:48][CH:49]=[C:43]([O:42][C:33]3[C:32]4[C:37](=[CH:38][C:39]([O:40][CH3:41])=[C:30]([O:29][CH3:28])[CH:31]=4)[N:36]=[CH:35][N:34]=3)[CH:44]=2)=[O:21])[N:9]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[N:8]=1)([CH3:6])[CH2:4][F:5]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 498410023-[(6,7-Dimethoxy-4-quinazolinyl)oxy]anilineHCID 66876857phenyl 3-(1,3-difluoro-2-methylpropan-2-yl)-1-phenyl-1H-pyrazol-5-ylcarbamate

Product 1

HCID 442428551-[3-(1,3-difluoro-2-methylpropan-2-yl)-1-phenyl-1H-pyrazol-5-yl]-3-[3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl]ureaYield 16%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Using the procedure described in Example 159B, phenyl 3-(1,3-difluoro-2-methylpropan-2-yl)-1-phenyl-1H-pyrazol-5-ylcarbamate from the previous step (0.186 g, 0.5 mmol) was reacted with 3-(6,7-dimethoxyquinazolin-4-yloxy)aniline from Example 113A (0.119 g, 0.4 mmol), and N,N-diisopropylethylamine (0.8 mL) in THF (6 mL) at 50° C. for 6 hours, to afford 1-[3-(1,3-difluoro-2-methylpropan-2-yl)-1-phenyl-1H-pyrazol-5-yl]-3-[3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl]urea as solid (0.037 g, 16%). 1H NMR (300 MHz, DMSO-d6) δ 9.16 (s, 1H), 8.54 (s, 2H), 7.56 (m, 7H), 7.50 (d, 1H), 7.38 (s, 1H), 7.22 (m, 2H), 6.54 (s, 1H), 4.73 (m, 2H), 4.58 (m, 2H), 3.99 (s, 3H), 3.97 (s, 3H), 1.33 (s, 3H); LC-MS (ESI) m/z 575 (M+H)+.

Sources & evidence

ORD record
ord-dd4b5744f790475a849688c81e18d3b9
Source dataset
uspto-grants-2016_04
Patent number
US09320739B2

Reaction notes

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