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Diisopropylethylamine → (3R,4R)-tert-butyl-4-methyl-3-((5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)methylcarbamoyl)piperidine-1-carboxylate

HRID 1969729
ノート
印刷プレビュー

反応式

HRID 1969729 の反応式
Cl.[S:2]([N:12]1[C:16]2=[N:17][CH:18]=[C:19]([CH2:21][NH2:22])[N:20]=[C:15]2[CH:14]=[CH:13]1)([C:5]1[CH:11]=[CH:10][C:8]([CH3:9])=[CH:7][CH:6]=1)(=[O:4])=[O:3].[C:23]([O:27][C:28]([N:30]1[CH2:35][CH2:34][C@@H:33]([CH3:36])[C@@H:32]([C:37](O)=[O:38])[CH2:31]1)=[O:29])([CH3:26])([CH3:25])[CH3:24].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[C:23]([O:27][C:28]([N:30]1[CH2:35][CH2:34][C@@H:33]([CH3:36])[C@@H:32]([C:37](=[O:38])[NH:22][CH2:21][C:19]2[N:20]=[C:15]3[CH:14]=[CH:13][N:12]([S:2]([C:5]4[CH:6]=[CH:7][C:8]([CH3:9])=[CH:10][CH:11]=4)(=[O:3])=[O:4])[C:16]3=[N:17][CH:18]=2)[CH2:31]1)=[O:29])([CH3:25])([CH3:26])[CH3:24]
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58557576(3R,4R)-1-(tert-butoxycarbonyl)-4-methylpiperidine-3-carboxylic acidHCID 67068339(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)methanamine hydrochloride

生成物 1

HCID 58557369
(3R,4R)-tert-butyl-4-methyl-3-((5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)methylcarbamoyl)piperidine-1-carboxylate
収率 100.4%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a slurry of (5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)methanamine hydrochloride (34.0 g, 100 mmol, Example #5, Step C), (3R,4R)-1-(tert-butoxycarbonyl)-4-methylpiperidine-3-carboxylic acid (24.43 g, 100 mmol) and HATU (38.2 g, 100 mmol) in DCM (700 mL) was added DIEA (52.6 mL, 301 mmol). The reaction was stirred at ambient temperature for about 45 min. The reaction was washed with saturated aqueous NaHCO3 (300 mL). The organic layer was separated, dried over anhydrous Na2SO4, filtered then concd in vacuo. The resulting residue was purified by chromatography on silica gel (330 g) using 33-100% EtOAc in heptane to give (3R,4R)-tert-butyl-4-methyl-3-((5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)methylcarbamoyl)piperidine-1-carboxylate (53 g, 100%) as a pale-yellow foam: LC/MS (Table 1, Method b) Rt=2.40 min; MS m/z: 528 (M+H)+.

後処理

  1. washThe reaction was washed with saturated aqueous NaHCO3 (300 mL)
  2. customThe organic layer was separated
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. customThe resulting residue was purified by chromatography on silica gel (330 g)

出典と根拠

ORDレコード
ord-0e941f5579cc4299b048aba2394248c0
出典データセット
uspto-grants-2013_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08426411B2

反応ノート

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