Cesium carbonate → 2[(2-fluorobenzyl)oxy]-5-(4-fluorophenyl)-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one

HRID 1396509ノート

反応式

HRID 1396509 の反応式
[F:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH2:4]Br.[F:10][C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH2:22][CH2:21][N:20]3[N:23]=[C:24]([OH:26])[CH:25]=[C:19]3[C:18]2=[O:27])=[CH:13][CH:12]=1.C([O-])([O-])=O.[Cs+].[Cs+]>C(#N)C>[F:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH2:4][O:26][C:24]1[CH:25]=[C:19]2[C:18](=[O:27])[N:17]([C:14]3[CH:13]=[CH:12][C:11]([F:10])=[CH:16][CH:15]=3)[CH2:22][CH2:21][N:20]2[N:23]=1

参加物

5

反応物 3

HCID 10796Cesium carbonateHCID 67968alpha-Bromo-o-fluorotolueneHCID 178515148HCID 178515148、化合物

生成物 1

HCID 727147862[(2-fluorobenzyl)oxy]-5-(4-fluorophenyl)-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one収率 85.2%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

2-Fluorobenzyl bromide (0.049 mL, 0.39 mmol) was added to a stirred suspension of 5-(4-fluorophenyl)-2-hydroxy-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one (0.092 g, 0.36 mmol) and Cs2CO3 (0.234 g, 0.72 mmol) in ACN (1.85 mL). The mixture was stirred at room temperature for 16 hours. The solvent was evaporated in vacuo. The residue was diluted with water and extracted with AcOEt. The organic layer was separated, washed with a saturated solution of NaCl, dried (Na2SO4), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; AcOEt in heptane 0/100 to 50/50). The desired fractions were collected and the solvents evaporated in vacuo to yield 2[(2-fluorobenzyl)oxy]-5-(4-fluorophenyl)-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one (0.109 g, 85% yield) as a white solid. C19H15F2N3O2. 1H NMR (500 MHz, CDCl3) δ ppm 4.14 (dd, J=6.8, 5.1 Hz, 2H), 4.37 (dd, J=6.9, 5.2 Hz, 2H), 5.30 (s, 2H), 6.37 (s, 1H), 7.04-7.15 (m, 3H), 7.17 (td, J=7.5, 0.9 Hz, 1H), 7.28-7.36 (m, 3H), 7.53 (td, J=7.4, 1.4 Hz, 1H).

後処理

  1. customThe solvent was evaporated in vacuo
  2. additionThe residue was diluted with water
  3. extractionextracted with AcOEt
  4. customThe organic layer was separated
  5. washwashed with a saturated solution of NaCl
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customthe solvents evaporated in vacuo
  9. customThe crude product was purified by flash column chromatography (silica; AcOEt in heptane 0/100 to 50/50)
  10. customThe desired fractions were collected
  11. customthe solvents evaporated in vacuo

出典と根拠

ORDレコード
ord-30417d5a5e404cd4812ecd1a025d1f39
出典データセット
uspto-grants-2014_12
特許番号
US08901125B2

反応ノート

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