3-(6,7-Dimethoxyquinazolin-4-yloxy)-2-fluoroaniline → 1-(3-tert-butyl-1-phenyl-1H-pyrazol-5-yl)-3-(3-(6,7-dimethoxyquinazolin-4-yloxy)-2-fluorophenyl)urea

HRID 1918069Notes

Reaction equation

HRID 1918069 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11](=[O:19])OC2C=CC=CC=2)[N:7]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:26][O:27][C:28]1[CH:29]=[C:30]2[C:35](=[CH:36][C:37]=1[O:38][CH3:39])[N:34]=[CH:33][N:32]=[C:31]2[O:40][C:41]1[C:42]([F:48])=[C:43]([CH:45]=[CH:46][CH:47]=1)[NH2:44]>C1COCC1>[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:44][C:43]2[CH:45]=[CH:46][CH:47]=[C:41]([O:40][C:31]3[C:30]4[C:35](=[CH:36][C:37]([O:38][CH3:39])=[C:28]([O:27][CH3:26])[CH:29]=4)[N:34]=[CH:33][N:32]=3)[C:42]=2[F:48])=[O:19])[N:7]([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[N:6]=1)([CH3:3])([CH3:2])[CH3:4]

Participants

4

Reactant 2

HCID 178195183-(6,7-Dimethoxyquinazolin-4-yloxy)-2-fluoroanilineHCID 46196894phenyl 3-tert-butyl-1-phenyl-1H-pyrazol-5-ylcarbamate

Product 1

HCID 442432271-(3-tert-butyl-1-phenyl-1H-pyrazol-5-yl)-3-(3-(6,7-dimethoxyquinazolin-4-yloxy)-2-fluorophenyl)ureaYield 63.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of phenyl 3-tert-butyl-1-phenyl-1H-pyrazol-5-ylcarbamate (prepared as described in Example 153A) (239 mg, 0.71 mmol), 3-(6,7-dimethoxyquinazolin-4-yloxy)-2-fluoroaniline (prepared as described in Example 265A steps 1 through 3) (150 mg, 0.475 mmol) and N,N-4-(dimethylamino)pyridine (10 mg, 0.082 mmol) in THF (5 mL) was stirred at rt for 15 h. The reaction mixture was concentrated under reduced pressure to give the crude product. Purification via silica gel flash chromatography (eluting with a gradient of 20% ethyl acetate in hexanes to 100% ethyl acetate) afforded 1-(3-tert-butyl-1-phenyl-1H-pyrazol-5-yl)-3-(3-(6,7-dimethoxyquinazolin-4-yloxy)-2-fluorophenyl)urea (167 mg, 63%) as a colorless solid. 1H NMR (300 MHz, DMSO-d6) δ 9.07 (brs, 1H), 8.85 (brs, 1H), 8.57 (s, 1H), 8.07 (m, 1H), 7.39-7.58 (m, 7H), 7.23 (m, 1H), 7.20 (m, 1H), 6.42 (s, 1H), 4.00 (s, 3H), 3.99 (s, 3H), 1.29 (s, 9H); LC-MS (ESI) m/z 557 (M+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customto give the crude product
  3. customPurification via silica gel flash chromatography (
  4. washeluting with a gradient of 20% ethyl acetate in hexanes to 100% ethyl acetate)

Sources & evidence

ORD record
ord-09e33e1590134d4b892193cdeb4425cf
Source dataset
uspto-grants-2013_12
Patent number
US08618289B2

Reaction notes

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