Tetrahydrofuran → HCID 136387813, compound

HRID 1043948Notes

Reaction equation

HRID 1043948 reaction equation
[O:1]1[CH2:6][CH:5]=[C:4]([C:7]2[CH:12]=[C:11]([CH3:13])[C:10]([C:14]3[CH:15]=[CH:16][C:17]4[C:18]5[N:38]([CH:39]6[CH2:44][CH2:43][O:42][CH2:41][CH2:40]6)[N:37]=[CH:36][C:19]=5[C:20](=[O:35])[N:21](CC5C=CC(OC)=CC=5OC)[C:22]=4[CH:23]=3)=[C:9]([CH3:45])[CH:8]=2)[CH2:3][CH2:2]1.C1COCC1.[H][H]>C(O)C.[C].[Pd]>[CH3:13][C:11]1[CH:12]=[C:7]([CH:4]2[CH2:3][CH2:2][O:1][CH2:6][CH2:5]2)[CH:8]=[C:9]([CH3:45])[C:10]=1[C:14]1[CH:15]=[CH:16][C:17]2[C:18]3[N:38]([CH:39]4[CH2:44][CH2:43][O:42][CH2:41][CH2:40]4)[N:37]=[CH:36][C:19]=3[C:20](=[O:35])[NH:21][C:22]=2[CH:23]=1

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 86686379HCID 86686379, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 136387813HCID 136387813, compoundYield 44.5%

Reagents, catalysts & solvents 2

HCID 178418390HCID 178418390, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

10% palladium carbon (50% wet, 15 mg) was added to a solution of 7-[4-(3,6-dihydro-2H-pyran-4-yl)-2,6-dimethylphenyl]-5-(2,4-dimethoxybenzyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one (44 mg) in ethanol (2 mL)-THF (2 mL). The reaction mixture was stirred at mom temperature for four hours and 35 minutes in a hydrogen atmosphere. The catalyst was removed from the reaction mixture by filtration, and the filtrate was then concentrated under reduced pressure. TFA (1.5 mL) was added to the resulting residue. The reaction mixture was stirred at 60° C. for 14 hours. The reaction mixture was returned to room temperature, and the reaction mixture was then concentrated under reduced pressure. Chloroform and a saturated aqueous sodium bicarbonate solution were added to the residue, and the organic layer was separated. The aqueous layer was re-extracted with chloroform. The combined organic layers were dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform 100%, then ethyl acetate 100%). The target fraction was collected and concentrated. Ethyl acetate and MTBE were added to the resulting residue. The precipitated solid was collected by filtration and dried under reduced pressure to give the title compound (14.8 mg).

Workup

  1. customThe catalyst was removed from the reaction mixture by filtration
  2. concentrationthe filtrate was then concentrated under reduced pressure
  3. additionTFA (1.5 mL) was added to the resulting residue
  4. customwas returned to room temperature
  5. concentrationthe reaction mixture was then concentrated under reduced pressure
  6. additionChloroform and a saturated aqueous sodium bicarbonate solution were added to the residue
  7. customthe organic layer was separated
  8. extractionThe aqueous layer was re-extracted with chloroform
  9. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe resulting residue was purified by silica gel column chromatography (chloroform 100%
  13. customThe target fraction was collected
  14. concentrationconcentrated
  15. additionEthyl acetate and MTBE were added to the resulting residue
  16. filtrationThe precipitated solid was collected by filtration
  17. customdried under reduced pressure

Sources & evidence

ORD record
ord-011585f68c9f4605a03a414c0c800ee7
Source dataset
uspto-grants-2013_10
Patent number
US08563565B2

Reaction notes

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