Water → (S)-6-Chloro-2-methyl-4-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)pyridazin-3(2H)-one

HRID 1185073ノート

反応式

HRID 1185073 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH2:22][CH2:21][NH:20][CH2:19][C@@H:18]3[CH3:23])=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1.[O:24]1[CH2:27][C:26](=O)[CH2:25]1.[BH3-]C#N.[Na+].O>CO.[Cl-].[Zn+2].[Cl-]>[Cl:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH2:22][CH2:21][N:20]([CH:26]4[CH2:27][O:24][CH2:25]4)[CH2:19][C@@H:18]3[CH3:23])=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1

参加物

7

反応物 4

HCID 962WaterHCID 5003444Sodium cyanoborohydrideHCID 150242543-OxetanoneHCID 86683945(S)-6-Chloro-2-methyl-4-(5-(2-methylpiperazin-1-yl)pyridin-2-ylamino)pyridazin-3(2H)-one

生成物 1

HCID 86683946(S)-6-Chloro-2-methyl-4-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)pyridazin-3(2H)-one収率 75.2%

試薬・触媒・溶媒 2

HCID 3007855Zincchloride触媒HCID 887Methanol溶媒

反応条件

温度
50 °C

実験手順

A mixture of 117b (2.3 g, 6.8 mmol), oxetan-3-one (1.4 g, 20.0 mmol), NaBH3CN (620 mg, 10 mmol), and zinc chloride (1.36 g, 10 mmol) in methanol (20 mL) was stirred at 50° C. for 3 hours. The mixture was added to water (40 mL) and concentrated under reduced pressure. The residue was extracted with dichloromethane three times. The combined organic layer was dried and concentrated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 50:1 dichloromethane/methanol to afford 117c (2.0 g, 75%). MS-ESI: [M+H]+ 391.2.

後処理

  1. concentrationconcentrated under reduced pressure
  2. extractionThe residue was extracted with dichloromethane three times
  3. customThe combined organic layer was dried
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica-gel column chromatography
  6. washeluting with 50:1 dichloromethane/methanol

出典と根拠

ORDレコード
ord-b90d6e6ca871410db57776d8591ea70c
出典データセット
uspto-grants-2014_03
特許番号
US08669251B2

反応ノート

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