Cesium carbonate → HCID 91100048, compound

HRID 631752Notes

Reaction equation

HRID 631752 reaction equation
FC1C=CC([NH:8][C:9]([NH:11][C:12]2[N:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[N:15]=[C:14]([C:23]([F:26])([F:25])[F:24])[CH:13]=2)=[O:10])=CC=1O.C([O-])([O-])=O.[Cs+].[Cs+].ClC1C2C(=CC(OC)=C(OC)C=2)N=CN=1>C1COCC1>[C:17]1([N:16]2[C:12]([NH:11][C:9](=[O:10])[NH2:8])=[CH:13][C:14]([C:23]([F:25])([F:26])[F:24])=[N:15]2)[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 27693644-Chloro-6,7-dimethoxyquinazolineHCID 66875903HCID 66875903, compound

Product 1

HCID 91100048HCID 91100048, compoundYield 40.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

After a mixture of 1-(4-fluoro-3-hydroxyphenyl)-3-(1-phenyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)urea (0.22 g, 0.58 mmol) and Cs2CO3 (0.325 g, 1 mmol) in THF (10 mL) was stirred at room temperature for 1 hour, to it was added 4-chloro-6,7-dimethoxyquinazoline (0.13 g, 0.58 mmol). It was stirred at 40° C. for 14 hours. The mixture was quenched by water and extracted with DCM. Extracts were dried over MgSO4 and concentrated. It was purified on a silica gel column using a mixture of EtOAc-hexane as eluent to give 14346,7-dimethoxyquinazolin-4-yloxy)-4-fluorophenyl)-3-(1-phenyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)urea (0.064 g, 19% yield). 1H NMR (300 MHz, DMSO-d6) δ 3.99 (s, 3H), 4.00 (s, 3H), 6.87 (s, 1H), 7.24 (m, 1H), 7.36 (t, 1H), 7.42 (s, 1H), 7.59 (m, 6H), 7.67 (dd, 1H), 8.56 (s, 1H), 8.83 (s, 1H), 9.32 (s, 1H); LC-MS (ESI) m/z 569 (M+H)+.

Workup

  1. stirringIt was stirred at 40° C. for 14 hours
  2. customThe mixture was quenched by water
  3. extractionextracted with DCM
  4. dry with materialExtracts were dried over MgSO4
  5. concentrationconcentrated
  6. customIt was purified on a silica gel column
  7. additiona mixture of EtOAc-hexane as eluent

Sources & evidence

ORD record
ord-daeaed96fa35441e99a7e90786bfb452
Source dataset
uspto-grants-2016_04
Patent number
US09320739B2

Reaction notes

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