Dimethylacetamide → 2-fluoro-5-[7-oxo-6-[4-(2-oxo-1-piperidinyl)phenyl]-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridin-1-yl]benzonitrile

HRID 491928노트

반응식

HRID 491928 반응식
Cl[C:2]1[CH:3]=[C:4]([N:9]2[C:13]3[C:14](=[O:31])[N:15]([C:18]4[CH:23]=[CH:22][C:21]([N:24]5[CH2:29][CH2:28][CH2:27][CH2:26][C:25]5=[O:30])=[CH:20][CH:19]=4)[CH2:16][CH2:17][C:12]=3[C:11]([C:32]([F:35])([F:34])[F:33])=[N:10]2)[CH:5]=[CH:6][C:7]=1[F:8].C[C:37]([N:39](C)C)=O>[C-]#N.[C-]#N.[Zn+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].[Zn]>[F:8][C:7]1[CH:6]=[CH:5][C:4]([N:9]2[C:13]3[C:14](=[O:31])[N:15]([C:18]4[CH:19]=[CH:20][C:21]([N:24]5[CH2:29][CH2:28][CH2:27][CH2:26][C:25]5=[O:30])=[CH:22][CH:23]=4)[CH2:16][CH2:17][C:12]=3[C:11]([C:32]([F:35])([F:34])[F:33])=[N:10]2)=[CH:3][C:2]=1[C:37]#[N:39]

참가 물질

7

반응물 2

HCID 31374DimethylacetamideHCID 102075641-(3-chloro-4-fluorophenyl)-6-[4-(2-oxo-1-piperidinyl)phenyl]-3-(trifluoromethyl)-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-one

생성물 1

HCID 222500932-fluoro-5-[7-oxo-6-[4-(2-oxo-1-piperidinyl)phenyl]-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridin-1-yl]benzonitrile수율 50%

시약·촉매·용매 4

HCID 11186Zinc cyanide (Zn(CN)2)촉매HCID 23994Zinc촉매HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)촉매HCID 9811564Bis(dibenzylideneacetone)palladium촉매

반응 조건

온도
140 °C

실험 절차

Part A. 1-(3-chloro-4-fluorophenyl)-6-[4-(2-oxo-1-piperidinyl)phenyl]-3-(trifluoromethyl)-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-one (0.35 g, 0.69 mmol), Zn(CN)2 (81 mg, 0.69 mmol), Pd2(dba)3 (63 mg, 0.07 mmol), dppf (77 mg, 0.14 mmol), and Zn (9 mg, 0.14 mmol) were added to 15 mL of DMAC. The mixture was degassed under argon and stirred at 140° C. under N2 for 12 h. The reaction was cooled to rt, ethylacetate (75 mL) was added and the mixture was filtered through Celite®. The filtrate was washed with saturated NaHCO3 solution (30 mL), water (30 mL×3), and brine (20 mL). It was then dried over Na2SO4, filtered, and concentrated. The residue was purified via flash chromatography on silica gel with 10% methanol in dichloromethane to give 2-fluoro-5-[7-oxo-6-[4-(2-oxo-1-piperidinyl)phenyl]-3-(trifluoromethyl)-4,5,6,7,-tetrahydro-1H-pyrazolo[3,4-c]pyridin-1-yl]benzonitrile (0.17 g, 50% yield). LRMS (AP+): 498.2 (M+H)+. 1H NMR (CDCl3) δ 7.91-7.85 (m, 2H), 7.31 (s, 4H), 7.28-7.25 (m, 1H), 4.16 (t, 2H), 3.63-3.61 (m, 2H), 3.18 (t, 2H), 2.56 (t, 2H), 1.96-1.93 (m, 4H).

후처리

  1. customThe mixture was degassed under argon
  2. temperatureThe reaction was cooled to rt
  3. additionethylacetate (75 mL) was added
  4. filtrationthe mixture was filtered through Celite®
  5. washThe filtrate was washed with saturated NaHCO3 solution (30 mL), water (30 mL×3), and brine (20 mL)
  6. dry with materialIt was then dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified via flash chromatography on silica gel with 10% methanol in dichloromethane

출처 및 근거

ORD 기록
ord-e907ed21ef8545b6b897e880e7cc8fe7
출처 데이터셋
uspto-grants-2009_05
특허 번호
US07531535B2

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