(3R)-3-Aminopiperidine, 3-BOC protected → tert-butyl (R)-1-(3-((R)-2-methoxypropanamido)-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

HRID 408406ノート

反応式

HRID 408406 の反応式
[NH:1]1[CH2:6][CH2:5][CH2:4][C@@H:3]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH2:2]1.Cl[C:16]1[C:21]([C:22]([F:25])([F:24])[F:23])=[CH:20][N:19]=[C:18]2[NH:26][CH:27]=[C:28]([NH:29][C:30](=[O:35])[C@H:31]([O:33][CH3:34])[CH3:32])[C:17]=12>CCCCO.O>[CH3:34][O:33][C@H:31]([CH3:32])[C:30]([NH:29][C:28]1[C:17]2[C:18](=[N:19][CH:20]=[C:21]([C:22]([F:25])([F:23])[F:24])[C:16]=2[N:1]2[CH2:6][CH2:5][CH2:4][C@@H:3]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:11])([CH3:13])[CH3:12])[CH2:2]2)[NH:26][CH:27]=1)=[O:35]

参加物

5

反応物 2

HCID 1514172(3R)-3-Aminopiperidine, 3-BOC protectedHCID 60205658HCID 60205658、化合物

生成物 1

HCID 60205659tert-butyl (R)-1-(3-((R)-2-methoxypropanamido)-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate収率 41%

試薬・触媒・溶媒 2

HCID 2631-Butanol溶媒HCID 962Water溶媒

反応条件

温度
160 °C

実験手順

(R)-tert-Butyl piperidin-3-ylcarbamate (456 mg, 2.28 mmol) and N,N-diispropylethylamine (294 mg, 0.396 mL, 2.28 mmol) were added to a suspension of (R)—N-(4-chloro-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-methoxypropanamide (244 mg, 0.759 mmol) in n-BuOH (3 mL). The resulting mixture was heated in a sealed tube under a nitrogen atmosphere at 160° C. for 24 hours. The cooled mixture was diluted with water and extracted with EtOAc (3×20 mL). The combined organic layer was dried over MgSO4 and filtered, and the filtrate was concentrated to an oil, which was purified by reverse phase chromatography (Biotage SP4, C-18 25M+, 15-80% CH3CN/water, 25CV) to give tert-butyl (R)-1-(3-((R)-2-methoxypropanamido)-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (151 mg, 41%) as a solid. LCMS (APCI+) m/z 386.1, 486.1 (M+H)+, Retention time=3.85 minutes.

後処理

  1. extractionextracted with EtOAc (3×20 mL)
  2. dry with materialThe combined organic layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationthe filtrate was concentrated to an oil, which
  5. customwas purified by reverse phase chromatography (Biotage SP4

出典と根拠

ORDレコード
ord-04af5462f0d84c6ea9e41a44ea936a7b
出典データセット
uspto-grants-2014_06
特許番号
US08758830B2

反応ノート

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