Cesium carbonate → 3-{6-[2-(2-Chloro-6-cyanophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridin-4-ylamino]-pyridin-3-yl}-azetidine-1-carboxylic acid tert-butyl ester

HRID 626761노트

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HRID 626761 반응식
Br[C:2]1[C:7]2=[CH:8][N:9]([C:11]3[C:18]([Cl:19])=[CH:17][CH:16]=[CH:15][C:12]=3[C:13]#[N:14])[N:10]=[C:6]2[C:5]([F:20])=[CH:4][N:3]=1.[C:21]([O:25][C:26]([N:28]1[CH2:31][CH:30]([C:32]2[CH:33]=[N:34][C:35]([NH2:38])=[CH:36][CH:37]=2)[CH2:29]1)=[O:27])([CH3:24])([CH3:23])[CH3:22].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.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]>[C:21]([O:25][C:26]([N:28]1[CH2:29][CH:30]([C:32]2[CH:33]=[N:34][C:35]([NH:38][C:2]3[C:7]4=[CH:8][N:9]([C:11]5[C:12]([C:13]#[N:14])=[CH:15][CH:16]=[CH:17][C:18]=5[Cl:19])[N:10]=[C:6]4[C:5]([F:20])=[CH:4][N:3]=3)=[CH:36][CH:37]=2)[CH2:31]1)=[O:27])([CH3:24])([CH3:22])[CH3:23]

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 58044110HCID 58044110, 화합물HCID 866970642-(4-Bromo-7-fluoropyrazolo[4,3-c]pyridin-2-yl)-3-chlorobenzonitrile

생성물 1

HCID 696749593-{6-[2-(2-Chloro-6-cyanophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridin-4-ylamino]-pyridin-3-yl}-azetidine-1-carboxylic acid tert-butyl ester수율 64.1%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

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온도
80 °C

실험 절차

A mixture of 2-(4-bromo-7-fluoropyrazolo[4,3-c]pyridin-2-yl)-3-chlorobenzonitrile (106 mg, 0.3 mmol), 3-(6-aminopyridin-3-yl)-azetidine-1-carboxylic acid tert-butyl ester (57 mg, 0.35 mmol), Pd2(dba)3 (7 mg, 0.0075 mmol), Xantphos (17 mg, 0.03 mmol) and cesium carbonate (196 mg, 0.6 mmol) in dioxane (3.0 mL) was degassed and purged with nitrogen. The reaction mixture was heated at 80° C. overnight. After cooling to room temperature, the resultant mixture was partitioned between ethyl acetate and water. The layers were separated and the organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (50-60% ethyl acetate in cyclohexane) to afford the title compound as a brown solid (100 mg, 64% yield). LCMS (Method C): RT=2.54 min, m/z: 520 [M+H+].

후처리

  1. customwas degassed
  2. custompurged with nitrogen
  3. temperatureAfter cooling to room temperature
  4. customthe resultant mixture was partitioned between ethyl acetate and water
  5. customThe layers were separated
  6. washthe organic layer was washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by silica gel flash chromatography (50-60% ethyl acetate in cyclohexane)

출처 및 근거

ORD 기록
ord-95ebeda07fc54d1a95430146ee79e568
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09309240B2

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