Cesium carbonate → 5-(2,4-dimethoxybenzyl)-7-(2-ethoxy-4-methylpyridin-3-yl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one

HRID 1043940ノート

反応式

HRID 1043940 の反応式
[CH3:1][O:2][C:3]1[CH:32]=[C:31]([O:33][CH3:34])[CH:30]=[CH:29][C:4]=1[CH2:5][N:6]1[C:15]2[CH:14]=[C:13](B(O)O)[CH:12]=[CH:11][C:10]=2[C:9]2[N:19]([CH:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)[N:20]=[CH:21][C:8]=2[C:7]1=[O:28].FC1C=C(C2C(OC)=NC(C)=CC=2C)C=CC=1C1N(C2CCOCC2)N=CC=1C(OCC)=O.Br[C:69]1[C:70]([O:76][CH2:77][CH3:78])=[N:71][CH:72]=[CH:73][C:74]=1[CH3:75].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.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.O>[CH3:1][O:2][C:3]1[CH:32]=[C:31]([O:33][CH3:34])[CH:30]=[CH:29][C:4]=1[CH2:5][N:6]1[C:15]2[CH:14]=[C:13]([C:69]3[C:70]([O:76][CH2:77][CH3:78])=[N:71][CH:72]=[CH:73][C:74]=3[CH3:75])[CH:12]=[CH:11][C:10]=2[C:9]2[N:19]([CH:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)[N:20]=[CH:21][C:8]=2[C:7]1=[O:28]

参加物

8

反応物 4

HCID 10796Cesium carbonateHCID 722123583-Bromo-2-ethoxy-4-methylpyridineHCID 86686363ethyl 5-[2-fluoro-4-(2-methoxy-4,6-dimethylpyridin-3-yl)phenyl]-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-carboxylateHCID 86686369[5-(2,4-dimethoxybenzyl)-4-oxo-1-(tetrahydro-2H-pyran-4-yl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-yl]boronic acid

生成物 1

HCID 866863685-(2,4-dimethoxybenzyl)-7-(2-ethoxy-4-methylpyridin-3-yl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

実験手順

[5-(2,4-dimethoxybenzyl)-4-oxo-1-(tetrahydro-2H-pyran-4-yl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-yl]boronic acid obtained in Preparation Example 1 (70 mg) was dissolved in 1,4-dioxane (4 mL). 3-bromo-2-ethoxy-4-methylpyridine obtained in Preparation Example 44 (49 mg), Pd(PPh3)4 (8.7 mg), cesium carbonate (148 mg) and water (1 mL) were added to the solution, and the mixture was reacted using a microwave reactor at 130° C. for two hours. The reaction mixture was returned to room temperature and then partitioned by adding ethyl acetate. The organic layer was washed with brine and then dried over magnesium sulfate. The desiccant was removed by filtration, and the filtrate was 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-ethoxy-4-methylpyridin-3-yl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one (55 mg). The 5-(2,4-dimethoxybenzyl)-7-(2-ethoxy-4-methylpyridin-3-yl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one (55 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 100%) to give the title compound (17 mg).

後処理

  1. additionwere added to the solution
  2. customthe mixture was reacted
  3. customat 130° C.
  4. customfor two hours
  5. customwas returned to room temperature
  6. custompartitioned
  7. additionby adding ethyl acetate
  8. washThe organic layer was washed with brine
  9. dry with materialdried over magnesium sulfate
  10. customThe desiccant was removed by filtration
  11. concentrationthe filtrate was concentrated under reduced pressure
  12. customThe resulting residue was purified by silica gel column chromatography (ethyl acetate/n-heptane, 30% to 50% to 80%)

出典と根拠

ORDレコード
ord-25ccd86e4e9f490dba1b1f493a357c75
出典データセット
uspto-grants-2013_10
特許番号
US08563565B2

反応ノート

読み込み中…