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 626761ノート

反応式

HRID 626761 の反応式
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]

参加物

7

反応物 4

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

生成物 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 ester収率 64.1%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

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+].

後処理

  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)

出典と根拠

ORDレコード
ord-95ebeda07fc54d1a95430146ee79e568
出典データセット
uspto-grants-2016_04
特許番号
US09309240B2

反応ノート

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