3-(6-Methoxy-7-(2-methoxyethoxy)quinazolin-4-yloxy)aniline → 1-[5-(1,3-Difluoro-2-methylpropan-2-yl)isoxazol-3-yl]-3-{3-[6-methoxy-7-(2-methoxyethoxy)quinazolin-4-yloxy]phenyl}urea

HRID 631531Notes

Reaction equation

HRID 631531 reaction equation
[F:1][CH2:2][C:3]([C:7]1[O:11][N:10]=[C:9]([NH:12][C:13](=[O:21])OC2C=CC=CC=2)[CH:8]=1)([CH3:6])[CH2:4][F:5].[CH3:22][O:23][C:24]1[CH:25]=[C:26]2[C:31](=[CH:32][C:33]=1[O:34][CH2:35][CH2:36][O:37][CH3:38])[N:30]=[CH:29][N:28]=[C:27]2[O:39][C:40]1[CH:41]=[C:42]([CH:44]=[CH:45][CH:46]=1)[NH2:43]>CN(C)C1C=CN=CC=1.C1COCC1>[F:5][CH2:4][C:3]([C:7]1[O:11][N:10]=[C:9]([NH:12][C:13]([NH:43][C:42]2[CH:44]=[CH:45][CH:46]=[C:40]([O:39][C:27]3[C:26]4[C:31](=[CH:32][C:33]([O:34][CH2:35][CH2:36][O:37][CH3:38])=[C:24]([O:23][CH3:22])[CH:25]=4)[N:30]=[CH:29][N:28]=3)[CH:41]=2)=[O:21])[CH:8]=1)([CH3:6])[CH2:2][F:1]

Participants

5

Reactant 2

HCID 668758053-(6-Methoxy-7-(2-methoxyethoxy)quinazolin-4-yloxy)anilineHCID 66876148Phenyl 5-(1,3-difluoro-2-methylpropan-2-yl)isoxazol-3-ylcarbamate

Product 1

HCID 582677951-[5-(1,3-Difluoro-2-methylpropan-2-yl)isoxazol-3-yl]-3-{3-[6-methoxy-7-(2-methoxyethoxy)quinazolin-4-yloxy]phenyl}ureaYield 37%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

The title compound was prepared as described in Example 162B, using phenyl 5-(1,3-difluoro-2-methylpropan-2-yl)isoxazol-3-ylcarbamate as described in Example 162A (0.089 g, 0.3 mmol), 3-(6-methoxy-7-(2-methoxyethoxy)quinazolin-4-yloxy)aniline from Example 117B (0.102 g, 0.3 mmol), and 4-(dimethylamino)pyridine (0.03 g) in THF (6 mL), to afford 1-[5-(1,3-difluoro-2-methylpropan-2-yl)isoxazol-3-yl]-3-{3-[6-methoxy-7-(2-methoxyethoxy)quinazolin-4-yloxy]phenyl}urea as solid (0.061 g, 37%). 1H NMR (300 MHz, DMSO-d6) δ 9.71 (s, 1H), 9.01 (s, 1H), 8.56 (s, 1H), 7.58 (m, 2H), 7.42 (m, 2H), 7.27 (d, 1H), 6.98 (d, 1H), 6.77 (s, 1H), 4.71 (s, 2H), 4.56 (s, 2H), 4.35 (m, 2H), 3.99 (s, 3H), 3.77 (m, 2H), 3.56 (s 3H), 1.28 (s, 3H); LC-MS (ESI) m/z 544 (M+H)+.

Workup

  1. customThe title compound was prepared

Sources & evidence

ORD record
ord-42e9edd2174b46e581fc17972af6d48f
Source dataset
uspto-grants-2016_04
Patent number
US09320739B2

Reaction notes

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