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4-Methoxypiperidine → N-(3-((4S,6S)-2-benzamido-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluorophenyl)-4-methoxypiperidine-1-carboxamide

HRID 930328
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HRID 930328 반응식
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([F:28])=[C:6]([C@:8]2([CH3:27])[CH2:13][C@@H:12]([C:14]([F:17])([F:16])[F:15])[O:11][C:10]([NH:18][C:19](=[O:26])[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[N:9]2)[CH:7]=1.Cl[C:30](OC1C=CC([N+]([O-])=O)=CC=1)=[O:31].[CH3:42][O:43][CH:44]1[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]1>ClCCl>[C:19]([NH:18][C:10]1[O:11][C@H:12]([C:14]([F:17])([F:15])[F:16])[CH2:13][C@:8]([C:6]2[CH:7]=[C:2]([NH:1][C:30]([N:47]3[CH2:48][CH2:49][CH:44]([O:43][CH3:42])[CH2:45][CH2:46]3)=[O:31])[CH:3]=[CH:4][C:5]=2[F:28])([CH3:27])[N:9]=1)(=[O:26])[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1
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참가 물질

5

반응물 3

HCID 776664-MethoxypiperidineHCID 821294-Nitrophenyl chloroformateHCID 86732123N-((4S,6S)-4-(5-amino-2-fluorophenyl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)benzamide

생성물 1

HCID 86732157N-(3-((4S,6S)-2-benzamido-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluorophenyl)-4-methoxypiperidine-1-carboxamide수율 61.1%

시약·촉매·용매 1

HCID 6344
Dichloromethane
용매

실험 절차

To a cooled (0° C.) solution of N-((4S,6S)-4-(5-amino-2-fluorophenyl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)benzamide (4l, 0.200 g, 0.506 mmol) in dichloromethane (4 mL) was added 4-nitrophenyl chloroformate (0.111 g, 0.551 mmol) as a solid. After 10 min the reaction was allowed to warm to room temperature. After 3 h 4-methoxy-piperidine (0.100 mL, 1.036 mmol) was added dropwise via syringe and the reaction was stirred overnight. The reaction was evaporated onto silica gel and purified by flash chromatography (Isco, 25 g) eluting with (25% EtOH/EtOAc):hexanes (0:1→2:3) to give N-(3-((4S,6S)-2-benzamido-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluorophenyl)-4-methoxypiperidine-1-carboxamide (166 mg. 61% yield) of a clear, colorless tar. MS m/z=537 [M+H]+. Calculated for C26H28F4N4O4: 536

후처리

  1. customThe reaction was evaporated onto silica gel
  2. custompurified by flash chromatography (Isco, 25 g)
  3. washeluting with (25% EtOH/EtOAc)

출처 및 근거

ORD 기록
ord-a419775cb47b47b9a22e3166984f357a
출처 데이터셋
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09296734B2

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