Cesium carbonate → HCID 56597557、化合物

HRID 475953

反応式

HRID 475953 の反応式
Cl[C:2]1[CH:3]=[C:4]([C:14]([NH:16][CH2:17][C:18]2[C:19](=[O:26])[NH:20][C:21]([CH3:25])=[CH:22][C:23]=2[CH3:24])=[O:15])[C:5]2[CH:10]=[N:9][N:8]([CH:11]([CH3:13])[CH3:12])[C:6]=2[N:7]=1.[N:27]1[CH:32]=[CH:31][C:30]([OH:33])=[CH:29][CH:28]=1.C(=O)([O-])[O-].[Cs+].[Cs+].N1C=CC=CC=1CC(=O)C>CS(C)=O.CCOC(C)=O.O.[Cu]Br>[CH3:24][C:23]1[CH:22]=[C:21]([CH3:25])[NH:20][C:19](=[O:26])[C:18]=1[CH2:17][NH:16][C:14]([C:4]1[C:5]2[CH:10]=[N:9][N:8]([CH:11]([CH3:13])[CH3:12])[C:6]=2[N:7]=[C:2]([O:33][C:30]2[CH:31]=[CH:32][N:27]=[CH:28][CH:29]=2)[CH:3]=1)=[O:15]

参加物

9

反応物 4

HCID 10796Cesium carbonateHCID 959101-(Pyridin-2-yl)propan-2-oneHCID 565974256-Chloro-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamideHCID 178418642HCID 178418642、化合物

生成物 1

HCID 56597557HCID 56597557、化合物

試薬・触媒・溶媒 4

HCID 24593copper(I) bromide触媒HCID 679Dimethyl Sulfoxide溶媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
110 °C

実験手順

6-Chloro-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide (0.15 g, 0.401 mmol), 4-pyridinol (0.057 g, 0.602 mmol), cesium carbonate (0.261 g, 0.802 mmol), and 1-(2-pyridinyl)-2-propanone (10.85 mg, 0.080 mmol) were sequentially dissolved in DMSO (4.0 mL). Next added copper(I) bromide (5.76 mg, 0.040 mmol) and the suspension was stirred under nitrogen (degassed) for 1 min. The sealed reaction mixture was stirred with heating at 110° C. (heating block) for 20 h, and then allowed to cool to room temperature overnight. The reaction mixture was diluted with EtOAc (25 mL) and water. The contents were vigorously stirred and then filtered through Celite, washing the filter pad with 20% THF/EtOAc. The layers were separated and the aq. layer extracted with EtOAc. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo to a dark residue that was dried under hi-vacuum overnight. The crude product was purified by silica gel chromatography (eluent: gradient of 5-95% Dichloromethane/Chloroform containing 2M Ammonia (in methanol). The collected product was washed with MTBE, filtered, and dried in a vacuum oven at 45° C. for 5 hr. The final product was collected as 0.075 g (42%). LCMS E-S (M+H)=433.2. 1H NMR (400 MHz, DMSO-d6) δ ppm 1H NMR (400 MHz, DMSO-d6) δ ppm 1.52 (d, J=6.57 Hz, 6H), 2.13 (s, 3H), 2.22 (s, 3H), 4.41 (d, J=5.05 Hz, 2H), 5.18-5.30 (m, 1H), 5.91 (s, 1H), 6.30-6.40 (m, 2H), 7.91 (s, 1H), 8.41 (s, 1H), 8.57-8.65 (m, 2H), 8.92 (t, J=4.93 Hz, 1H), 11.58 (s, 1H).

後処理

  1. customThe sealed reaction mixture
  2. stirringwas stirred
  3. temperature(heating block) for 20 h
  4. temperatureto cool to room temperature overnight
  5. stirringThe contents were vigorously stirred
  6. filtrationfiltered through Celite
  7. washwashing the filter pad with 20% THF/EtOAc
  8. customThe layers were separated
  9. extractionthe aq. layer extracted with EtOAc
  10. dry with materialThe combined organic layers were dried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo to a dark residue that
  13. customwas dried under hi-vacuum overnight
  14. customThe crude product was purified by silica gel chromatography (eluent
  15. washThe collected product was washed with MTBE
  16. filtrationfiltered
  17. customdried in a vacuum oven at 45° C. for 5 hr
  18. customThe final product was collected as 0.075 g (42%)

出典と根拠

ORDレコード
ord-7648a33b80784af593d8dabd2f920546
出典データセット
uspto-grants-2014_01
特許番号
US08637509B2

関連ノート

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