Morpholine → tert-butyl ((2S,4R)-1-acetyl-2-methyl-6-(5-(morpholine-4-carbonyl)pyridin-2-yl)-1,2,3,4-tetrahydroquinolin-4-yl)carbamate

HRID 882263노트

반응식

HRID 882263 반응식
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:22]=[CH:21][C:17]([C:18]([OH:20])=O)=[CH:16][N:15]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:6][C@@H:5]1[CH3:31])(=[O:3])[CH3:2].[NH:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1.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>CN(C=O)C>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:22]=[CH:21][C:17]([C:18]([N:32]4[CH2:37][CH2:36][O:35][CH2:34][CH2:33]4)=[O:20])=[CH:16][N:15]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:23][C:24](=[O:25])[O:26][C:27]([CH3:30])([CH3:28])[CH3:29])[CH2:6][C@@H:5]1[CH3:31])(=[O:3])[CH3:2]

참가 물질

6

반응물 4

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 867094306-((2S,4R)-1-acetyl-4-((tert-butoxycarbonyl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)nicotinic acid

생성물 1

HCID 86709431tert-butyl ((2S,4R)-1-acetyl-2-methyl-6-(5-(morpholine-4-carbonyl)pyridin-2-yl)-1,2,3,4-tetrahydroquinolin-4-yl)carbamate수율 86%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

6-((2S,4R)-1-acetyl-4-((tert-butoxycarbonyl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)nicotinic acid (for a preparation, see Intermediate 63) (2.05 g, 4.82 mmol), morpholine (2.084 mL, 24.09 mmol), HATU (2.015 g, 5.30 mmol) and DIPEA (2.52 mL, 14.45 mmol) were combined in DMF (25 mL) and the reaction stirred at room temperature for 90 mins. The mixture was concentrated in vacuo before being dissolved in DCM and loaded onto an aminopropyl SPE column (70 g). The column was eluted with 10% MeOH in DCM, and the appropriate fractions combined and concentrated to dryness in cavuo. The residue was purified by chromatography (100 g column, EtOAc/cyclohexane gradient) to give tert-butyl ((2S,4R)-1-acetyl-2-methyl-6-(5-(morpholine-4-carbonyl)pyridin-2-yl)-1,2,3,4-tetrahydroquinolin-4-yl)carbamate (2.05 g, 4.14 mmol, 86% yield).

후처리

  1. concentrationThe mixture was concentrated in vacuo
  2. dissolutionbefore being dissolved in DCM
  3. washThe column was eluted with 10% MeOH in DCM
  4. concentrationconcentrated to dryness in cavuo
  5. customThe residue was purified by chromatography (100 g column, EtOAc/cyclohexane gradient)

출처 및 근거

ORD 기록
ord-51943cf29d644bc88272cbdb6d13ee0a
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08993554B2

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