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 1043933ノート

反応式

HRID 1043933 の反応式
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

参加物

3

反応物 1

HCID 866863555-(2,4-dimethoxybenzyl)-7-(2,6-dimethylphenyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one

生成物 1

HCID 1363878087-(2,6-dimethylphenyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one収率 18.7%

試薬・触媒・溶媒 1

HCID 6422Trifluoroacetic acid溶媒

反応条件

温度
65 °C

実験手順

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).

後処理

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

出典と根拠

ORDレコード
ord-3252c6cd86114e68b615a9b06e67e20d
出典データセット
uspto-grants-2013_10
特許番号
US08563565B2

反応ノート

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