5-(2,4-dimethoxybenzyl)-7-(2,6-dimethylphenyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one → 7-(2,6-dimethylphenyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one

HRID 1043933Notes

Reaction equation

COC1C=C(OC)C=CC=1C[N:6]1[C:15]2[CH:14]=[C:13]([C:16]3[C:21]([CH3:22])=[CH:20][CH:19]=[CH:18][C:17]=3[CH3:23])[CH:12]=[CH:11][C:10]=2[C:9]2[N:24]([CH:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)[N:25]=[CH:26][C:8]=2[C:7]1=[O:33]>C(O)(C(F)(F)F)=O>[CH3:22][C:21]1[CH:20]=[CH:19][CH:18]=[C:17]([CH3:23])[C:16]=1[C:13]1[CH:12]=[CH:11][C:10]2[C:9]3[N:24]([CH:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)[N:25]=[CH:26][C:8]=3[C:7](=[O:33])[NH:6][C:15]=2[CH:14]=1

Participants

Conditions

Temperature: 65 °C

Procedure

7-chloro-5-(2,4-dimethoxybenzyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one obtained in Preparation Example 2 (100 mg) was dissolved in DMF (3.3 mL). 2,6-dimethylphenylboronic acid (33 mg), Pd(PPh3)4 (13 mg), potassium carbonate (91 mg) and water (0.7 mL) were added to the solution, and the mixture was reacted using a microwave reactor at 150° C. for two hours. The reaction mixture was returned to room temperature and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate/n-heptane, 30% to 50% to 80%) to give 5-(2,4-dimethoxybenzyl)-7-(2,6-dimethylphenyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one (80 mg). The 5-(2,4-dimethoxybenzyl)-7-(2,6-dimethylphenyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one (75 mg) was dissolved in TFA. (1 mL), and the mixture was stirred at 65° C. for two hours. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. The resulting residue was neutralized by adding a saturated aqueous sodium bicarbonate solution. The aqueous solution was extracted with DCM. The organic layer was dried over anhydrous magnesium sulfate. The desiccant was removed by filtration. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate/n-heptane, 50% to 70% to 80%) to give the title compound (10 mg).

Workup

temperatureThe reaction mixture was cooled to room temperature
concentrationconcentrated under reduced pressure
additionby adding a saturated aqueous sodium bicarbonate solution
extractionThe aqueous solution was extracted with DCM
dry with materialThe organic layer was dried over anhydrous magnesium sulfate
customThe desiccant was removed by filtration
concentrationThe filtrate was concentrated under reduced pressure
customThe resulting residue was purified by silica gel column chromatography (ethyl acetate/n-heptane, 50% to 70% to 80%)

Sources & evidence

ORD record: ord-3252c6cd86114e68b615a9b06e67e20d
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08563565B2

Reaction notes

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