Dimethyl Sulfoxide → 1-[1-(quinolin-6-ylmethyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl]pyrrolidin-3-one

HRID 16008

反応式

HRID 16008 の反応式
C(Cl)(=O)C(Cl)=O.CS(C)=O.[N:11]1[C:20]2[C:15](=[CH:16][C:17]([CH2:21][N:22]3[C:26]4=[N:27][C:28]([N:31]5[CH2:35][CH2:34][CH:33]([OH:36])[CH2:32]5)=[CH:29][N:30]=[C:25]4[N:24]=[N:23]3)=[CH:18][CH:19]=2)[CH:14]=[CH:13][CH:12]=1.C(N(CC)CC)C>ClCCl>[N:11]1[C:20]2[C:15](=[CH:16][C:17]([CH2:21][N:22]3[C:26]4=[N:27][C:28]([N:31]5[CH2:35][CH2:34][C:33](=[O:36])[CH2:32]5)=[CH:29][N:30]=[C:25]4[N:24]=[N:23]3)=[CH:18][CH:19]=2)[CH:14]=[CH:13][CH:12]=1

参加物

6

反応物 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 593418001-[1-(quinolin-6-ylmethyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl]pyrrolidin-3-ol

生成物 1

HCID 593418151-[1-(quinolin-6-ylmethyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl]pyrrolidin-3-one収率 40.3%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

To a cooled (−78° C.) solution of oxalyl chloride (1.5 mL, 17 mmol) in dichloromethane (15 mL) was added dimethyl sulfoxide (2.45 mL, 34.5 mmol) drop wise keeping T<−70° C. After 30 minutes, a suspension of 1-[1-(quinolin-6-ylmethyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl]pyrrolidin-3-ol (1.00 g, 2.88 mmol) in dichloromethane (35 mL) was added keeping T<−70° C. After 1 hour 15 minutes, triethylamine (3.61 mL, 25.9 mmol) was added slowly, the dry-ice bath was removed, and the reaction was stirred for 2 hours. The reaction was quenched with water (50 mL), diluted with dichloromethane (150 ml), and separated. The aqueous layer was extracted with dichloromethane (2×50 mL) and the organics were combined and concentrated. The crude product was purified by flash chromatography using a Horizon purification system on a 40M column eluting with chloroform/methanol (0.5-8%) to afford 1-[1-(quinolin-6-ylmethyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl]pyrrolidin-3-one (401 mg, 40%).

後処理

  1. additionwas added
  2. customT<−70° C
  3. customthe dry-ice bath was removed
  4. customThe reaction was quenched with water (50 mL)
  5. additiondiluted with dichloromethane (150 ml)
  6. customseparated
  7. extractionThe aqueous layer was extracted with dichloromethane (2×50 mL)
  8. concentrationconcentrated
  9. customThe crude product was purified by flash chromatography
  10. customa Horizon purification system on a 40M column
  11. washeluting with chloroform/methanol (0.5-8%)

出典と根拠

ORDレコード
ord-545560e088204b878f56f4bedb93e92e
出典データセット
uspto-grants-2010_06
特許番号
US07732604B2

関連ノート

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