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Diisopropylethylamine → 4-(3-{(R)-3-[1-(4-hydroxy-phenyl)-2-methoxycarbonyl-ethylcarbamoyl]-piperidin-1-yl}-3-oxo-propyl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 526317
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HRID 526317 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][C:16]([N:18]2[CH2:23][CH2:22][CH2:21][C@@H:20]([C:24](O)=[O:25])[CH2:19]2)=[O:17])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:51][O:52][C:53](=[O:64])[CH2:54][CH:55]([NH2:63])[C:56]1[CH:61]=[CH:60][C:59]([OH:62])=[CH:58][CH:57]=1.C(N(C(C)C)C(C)C)C>CN(C)C=O.O>[OH:62][C:59]1[CH:60]=[CH:61][C:56]([CH:55]([NH:63][C:24]([C@@H:20]2[CH2:21][CH2:22][CH2:23][N:18]([C:16](=[O:17])[CH2:15][CH2:14][CH:11]3[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])[CH2:9][CH2:10]3)[CH2:19]2)=[O:25])[CH2:54][C:53]([O:52][CH3:51])=[O:64])=[CH:57][CH:58]=1
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참가 물질

7

반응물 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 54408184(R)-1-(3-(1-tert-butoxycarbonyl-4-piperidyl)propionyl]-3-piperidinecarboxylic acid2회HCID 58961718Methyl 3-Amino-3-(4-hydroxyphenyl)propanoate

생성물 1

HCID 71259020
4-(3-{(R)-3-[1-(4-hydroxy-phenyl)-2-methoxycarbonyl-ethylcarbamoyl]-piperidin-1-yl}-3-oxo-propyl)-piperidine-1-carboxylic acid tert-butyl ester
수율 85.2%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매2회

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온도
0 °C

실험 절차

490.75 mg (1.33 mmol) (3R)-1-{3-[1-(tert-butoxycarbonyl)piperidin-4-yl]propanoyl}piperidine-3-carboxylic acid (Bioorg. Med. Chem. 13 (2005) 4343-4352, Compound 10) were suspended in 8 ml N,N-dimethylformamide and cooled to 0° C. 0.545 g (1.43 mmol) HATU, a solution of 200.0 mg (1.0 mmol) 3-amino-3-(4-hydroxy-phenyl)-propionic acid methyl ester in 12 ml N,N-dimethylformamide and 0.53 ml (3.07 mmol) N-ethyl-diisopropylamine were added. The mixture was stirred at 0° C. for 5 minutes and at room temperature for 24 hours. 20 ml water were added and the mixture extracted with dichloromethane, washed with saturated sodium chloride solution, dried over sodium sulfate and concentrated in vacuum. Chromatography over 28 g basic silica gel (dichloromethane/ethanol 100/0-95/5-90/10-80/20) gave 465 mg (83%) tert-butyl 4-[3-((3R)-3-{[1-(4-hydroxyphenyl)-3-methoxy-3-oxopropyl]carbamoyl}piperidin-1-yl)-3-oxopropyl]piperidine-1-carboxylate.

후처리

  1. extractionthe mixture extracted with dichloromethane
  2. washwashed with saturated sodium chloride solution
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuum

출처 및 근거

ORD 기록
ord-c8707850eee749d588bebe38f8ee57f9
출처 데이터셋
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09345793B2

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