Hydrochloric Acid → (3R,4R)-tert-butyl 3-(6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)-4-methyl-piperidine-1-carboxylate

HRID 1969592ノート

反応式

HRID 1969592 の反応式
[CH3:1][C@@H:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][C@@H:3]1[C:15]1[N:19]2[C:20]3[CH:26]=[CH:25][N:24](S(C4C=CC(C)=CC=4)(=O)=O)[C:21]=3[N:22]=[CH:23][C:18]2=[CH:17][N:16]=1.[OH-].[Na+].Cl>O1CCOCC1>[C:15]1([C@@H:3]2[C@H:2]([CH3:1])[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:12])([CH3:14])[CH3:13])=[O:9])[CH2:4]2)[N:19]2[C:20]3[CH:26]=[CH:25][NH:24][C:21]=3[N:22]=[CH:23][C:18]2=[CH:17][N:16]=1

参加物

5

反応物 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 58557067(3R,4R)-tert-butyl 4-methyl-3-(6-tosyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)piperidine-1-carboxylate

生成物 1

HCID 58557258(3R,4R)-tert-butyl 3-(6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)-4-methyl-piperidine-1-carboxylate収率 108.2%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
60 °C

実験手順

To a solution of (3R,4R)-tert-butyl 4-methyl-3-(6-tosyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)piperidine-1-carboxylate (40 g, 78 mmol, Example #5 Step H) in 1,4-dioxane (160 mL) was added NaOH (1 N aqueous, 157 mL). The reaction was heated at about 60° C. for about 1 h. The reaction was allowed to cool to ambient temperature. The reaction was neutralized with aqueous HCl (4 N, 50 mL). The layers and extracted with DCM (2×300 mL). The combined organic extracts were washed with brine (400 mL), dried over anhydrous Na2SO4, filtered then concd in vacuo. The product was purified by chromatography on silica gel (330 g) using 1-5% MeOH in DCM to give (3R,4R)-tert-butyl 3-(6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)-4-methylpiperidine-1-carboxylate (30 g, 99%): LC/MS (Table 1, Method b) Rt=2.00 min; MS m/z: 356 (M+H)+.

後処理

  1. temperatureto cool to ambient temperature
  2. extractionThe layers and extracted with DCM (2×300 mL)
  3. washThe combined organic extracts were washed with brine (400 mL)
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. customThe product was purified by chromatography on silica gel (330 g)

出典と根拠

ORDレコード
ord-555d03b05a4647b38f597d0caad4f856
出典データセット
uspto-grants-2013_04
特許番号
US08426411B2

反応ノート

読み込み中…