Hydrochloric Acid → HCID 136337171, compound

HRID 1428846Notes

Reaction equation

HRID 1428846 reaction equation
CCOCC.[CH:6]1([Mg]Cl)[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]1.[CH2:14]([O:16][C:17]([C:19]1[CH:20]=[N:21][N:22]([C:24]2[NH:33][C:32](=[O:34])[C:31]3[C:26](=[CH:27][C:28]([F:36])=[C:29](Br)[CH:30]=3)[N:25]=2)[CH:23]=1)=[O:18])[CH3:15].Cl>[Cl-].[Cl-].[Zn+2].C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CCO.C1COCC1>[CH2:14]([O:16][C:17]([C:19]1[CH:20]=[N:21][N:22]([C:24]2[NH:33][C:32](=[O:34])[C:31]3[C:26](=[CH:27][C:28]([F:36])=[C:29]([CH:6]4[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]4)[CH:30]=3)[N:25]=2)[CH:23]=1)=[O:18])[CH3:15]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 3283Diethyl Ether2×HCID 136337172HCID 136337172, compoundHCID 178478990HCID 178478990, compound

Product 1

HCID 136337171HCID 136337171, compoundYield 54%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 3007855ZincchlorideCatalystHCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To THF (5 mL), a 1M solution of ZnCl2 in ether (5.00 mL, 5.00 mmol) was added followed by a 2M solution of cyclohexyl magnesium chloride in ether (2.50 mL, 5.00 mmol). The reaction mixture was stirred overnight at room temperature and the stirring was stopped until all of the precipitate settled to the bottom of the flask. In a different flask, THF (4 mL) was added to a mixture of palladium acetate (11.8 mg, 0.053 mmol), Ru-Phos (48.9 mg, 0.105 mmol) and 1-(6-bromo-7-fluoro-4-oxo-3,4-dihydro-quinazolin-2-yl)-1H-pyrazole-4-carboxylic acid ethyl ester (0.200 g, 0.525 mmol) and purged with nitrogen for 5 minutes. Then, a solution of cyclohexyl zinc chloride prepared as described above (5.25 mL, 2.62 mmol) was added and the mixture stirred for 18 h. The crude reaction mixture was poured into EtOH (10 mL) and acidified with 6 M aq. HCl (1 mL) slowly. The precipitated product was collected by filtration, triturated with EtOH and filtered again to provide the titled compound (0.110 g, 54%). MS (ESI/Cl): mass calcd. for C20H21FN4O3, 384.2; m/z found, 385.2 [M+H]+.

Workup

  1. custompurged with nitrogen for 5 minutes
  2. customThen, a solution of cyclohexyl zinc chloride prepared
  3. additionwas added
  4. stirringthe mixture stirred for 18 h
  5. customThe crude reaction mixture
  6. filtrationThe precipitated product was collected by filtration
  7. customtriturated with EtOH
  8. filtrationfiltered again

Sources & evidence

ORD record
ord-93575da67ab042ff9eb200b0ee241761
Source dataset
uspto-grants-2015_01
Patent number
US08937078B2

Reaction notes

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