Sodium hydride → Ethyl 5-(cyclopropylmethyl)-4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxylate

HRID 2046205ノート

反応式

HRID 2046205 の反応式
[H-].[Na+].[CH2:3]([O:5][C:6]([C:8]1[CH:17]=[C:11]2[C:12](=[O:16])[NH:13][CH2:14][CH2:15][N:10]2[N:9]=1)=[O:7])[CH3:4].Br[CH2:19][CH:20]1[CH2:22][CH2:21]1>CN(C=O)C.O>[CH2:3]([O:5][C:6]([C:8]1[CH:17]=[C:11]2[C:12](=[O:16])[N:13]([CH2:19][CH:20]3[CH2:22][CH2:21]3)[CH2:14][CH2:15][N:10]2[N:9]=1)=[O:7])[CH3:4]

参加物

6

反応物 3

HCID 24758Sodium hydrideHCID 81503BromomethylcyclopropaneHCID 42873667Ethyl 4-oxo-4,5,6,7-tetrahydropyrazolo(1,5-a)pyrazine-2-carboxylate

生成物 1

HCID 58465837Ethyl 5-(cyclopropylmethyl)-4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxylate収率 54%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

A 60% dispersion of sodium hydride in mineral oils (0.11 g, 2.74 mmol) was added to a stirred solution of 4,5,6,7-tetrahydro-4-oxo-pyrazolo[1,5-a]pyrazine-2-carboxylic acid ethyl ester (0.48 g, 2.28 mmol) in DMF (11.4 mL) at 0° C. The mixture was stirred at room temperature for 15 minutes and then bromomethylcyclopropane (0.26 mL, 2.74 mmol) was added. The mixture was stirred at room temperature for 16 hours, diluted with water and extracted with AcOEt. The organic layer was separated, washed with brine, dried (NaSO4), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 40/60). The desired fractions were collected and the solvents evaporated in vacuo to yield 5-cyclopropylmethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo[1,5-a]pyrazine-2-carboxylic acid ethyl ester (0.32 g, 54% yield) as a white solid.

後処理

  1. stirringThe mixture was stirred at room temperature for 16 hours
  2. extractionextracted with AcOEt
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried (NaSO4)
  6. filtrationfiltered
  7. customthe solvents evaporated in vacuo
  8. customThe crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 40/60)
  9. customThe desired fractions were collected
  10. customthe solvents evaporated in vacuo

出典と根拠

ORDレコード
ord-489246cdae734bb3b130925375f74b32
出典データセット
uspto-grants-2013_11
特許番号
US08592422B2

反応ノート

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