Cesium carbonate → 3-[({5-[(4-Fluorophenyl)carbonyl]-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-yl}oxy)methyl]benzonitrile

HRID 571732

反応式

HRID 571732 の反応式
Br[CH2:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=1)[C:6]#[N:7].[F:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]([N:20]2[CH2:25][CH2:24][N:23]3[N:26]=[C:27]([OH:29])[CH:28]=[C:22]3[CH2:21]2)=[O:19])=[CH:14][CH:13]=1.C([O-])([O-])=O.[Cs+].[Cs+]>C(#N)C.O>[F:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]([N:20]2[CH2:25][CH2:24][N:23]3[N:26]=[C:27]([O:29][CH2:2][C:3]4[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=4)[C:6]#[N:7])[CH:28]=[C:22]3[CH2:21]2)=[O:19])=[CH:14][CH:13]=1

参加物

6

反応物 3

HCID 10796Cesium carbonateHCID 97249Benzonitrile, 3-(bromomethyl)-HCID 178519627HCID 178519627、化合物

生成物 1

HCID 727032163-[({5-[(4-Fluorophenyl)carbonyl]-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-yl}oxy)methyl]benzonitrile収率 59.1%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6342Acetonitrile溶媒

実験手順

3-(bromomethyl)benzonitrile (0.086 g, 0.44 mmol) was added to a stirred suspension of 5-[(4-fluorophenyl)carbonyl]-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ol (0.105 g, 0.4 mmol) and Cs2CO3 (0.261 g, 0.8 mmol) in ACN (2 mL). The mixture was stirred at room temperature for 16 hours, then diluted with water and extracted with DCM. The organic layer was separated, dried (MgSO4), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 50/50). The desired fractions were collected, the solvents evaporated in vacuo and the residue triturated with DIPE to yield 3-[({5-[(4-fluorophenyl)carbonyl]-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-yl}oxy)methyl]benzonitrile (0.089 g, 59% yield) as a white solid. C21H17FN4O2. 1H NMR (500 MHz, CDCl3) δ ppm 4.08 (br. s., 4 H), 4.74 (br. s., 2 H), 5.22 (s, 2 H), 5.51 (br. s., 1 H), 7.15 (t, J=8.5 Hz, 2 H), 7.44-7.51 (m, 3 H), 7.60 (d, J=7.8 Hz, 1 H), 7.65 (d, J=7.8 Hz, 1 H), 7.74 (s, 1 H).

後処理

  1. extractionextracted with DCM
  2. customThe organic layer was separated
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. customthe solvents evaporated in vacuo
  6. customThe crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 50/50)
  7. customThe desired fractions were collected
  8. customthe solvents evaporated in vacuo
  9. customthe residue triturated with DIPE

出典と根拠

ORDレコード
ord-01c8c94e1b9646b7944fc260fa3cbca8
出典データセット
uspto-grants-2015_05
特許番号
US09029366B2

関連ノート

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