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 1043940노트

반응식

HRID 1043940 반응식
[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]

참가 물질

8

반응물 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

생성물 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

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 312751,4-Dioxane용매

실험 절차

[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).

후처리

  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%)

출처 및 근거

ORD 기록
ord-25ccd86e4e9f490dba1b1f493a357c75
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08563565B2

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