Cesium carbonate → HCID 58267719, compound

HRID 1918190Notes

Reaction equation

HRID 1918190 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([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])=[CH:4][C:3]=1[OH:27].C([O-])([O-])=O.[Cs+].[Cs+].Cl[C:35]1[C:44]2[C:39](=[CH:40][C:41]([O:47][CH3:48])=[C:42]([O:45][CH3:46])[CH:43]=2)[N:38]=[CH:37][N:36]=1>C1COCC1>[CH3:46][O:45][C:42]1[CH:43]=[C:44]2[C:39](=[CH:40][C:41]=1[O:47][CH3:48])[N:38]=[CH:37][N:36]=[C:35]2[O:27][C:3]1[CH:4]=[C:5]([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:24])([F:25])[F:26])[CH:13]=2)=[O:10])[CH:6]=[CH:7][C:2]=1[F:1]

Participants

5

Reactant 3

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

Product 1

HCID 58267719HCID 58267719, compoundYield 19.4%

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 1-(3-(6,7-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) 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-4da6cb76055a461a95a809cc479da85a
Source dataset
uspto-grants-2013_12
Patent number
US08618289B2

Reaction notes

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