Tetrahydrofuran → Ethyl 8-benzyl-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxylate

HRID 44578Notes

Reaction equation

HRID 44578 reaction equation
[Br-].[CH2:2]([Zn+])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C1COCC1.[CH3:15][N:16]1[C:28]2[C:27]3[N:26]=[C:25](SC)[N:24]=[CH:23][C:22]=3[CH2:21][CH2:20][C:19]=2[C:18]([C:31]([O:33][CH2:34][CH3:35])=[O:32])=[N:17]1.C(=O)(O)[O-].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(OCC)(=O)C>[CH2:2]([C:25]1[N:24]=[CH:23][C:22]2[CH2:21][CH2:20][C:19]3[C:18]([C:31]([O:33][CH2:34][CH3:35])=[O:32])=[N:17][N:16]([CH3:15])[C:28]=3[C:27]=2[N:26]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 516892Sodium BicarbonateHCID 45141606Ethyl 1-methyl-8-(methylthio)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxylateHCID 178419772HCID 178419772, compound

Product 1

HCID 57444089Ethyl 8-benzyl-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxylate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

Under a nitrogen atmosphere, a 0.5 M solution of benzylzinc bromide in THF (3.11 mL, 1.556 mmol) was added to a mixture of ethyl 1-methyl-8-(methylthio)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxylate (237 mg, 0.778 mmol) and Pd(PPh3)4 (9 mg, 0.0078 mmol, 1%). After 20 hours of heating at 60° C. under nitrogen, the mixture was cooled to room temperature, shaken with aqueous sodium bicarbonate and ethyl acetate and then filtered. The organic phase was then separated and the aqueous phase was extracted twice with ethyl acetate. The combined organic phase was dried over Na2SO4, evaporated and the crude was purified on silica gel (eluant dichloromethane/methanol 97/3). 20 mg of the title compound were isolated.

Workup

  1. temperaturethe mixture was cooled to room temperature
  2. filtrationfiltered
  3. customThe organic phase was then separated
  4. extractionthe aqueous phase was extracted twice with ethyl acetate
  5. dry with materialThe combined organic phase was dried over Na2SO4
  6. customevaporated
  7. customthe crude was purified on silica gel (eluant dichloromethane/methanol 97/3)

Sources & evidence

ORD record
ord-475b44fef5ce421d944ce6f3bf525cce
Source dataset
uspto-grants-2013_09
Patent number
US08541429B2

Reaction notes

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