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 882263ノート

反応式

HRID 882263 の反応式
[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]

参加物

6

反応物 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

生成物 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)carbamate収率 86%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-51943cf29d644bc88272cbdb6d13ee0a
出典データセット
uspto-grants-2015_03
特許番号
US08993554B2

反応ノート

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