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Trifluoroacetic acid → methyl 2-((R)-(3-chlorophenyl)((R)-1-((S)-1-(N-Methyl-2-(trimethylsilyl)ethoxycarbonylamino)-3-((R)-tetrahydro-2H-pyran-3-yl)propan-2-ylcarbamoyl)piperidin-3-yl)methoxy)ethylcarbamate

HRID 452014
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HRID 452014 반응식
[NH2:1][C@@H:2]([CH2:15][C@H:16]1[CH2:21][CH2:20][CH2:19][O:18][CH2:17]1)[CH2:3][N:4]([CH3:14])[C:5](=[O:13])[O:6][CH2:7][CH2:8][Si:9]([CH3:12])([CH3:11])[CH3:10].CCN(C(C)C)C(C)C.C1N=CN([C:36]([N:38]2[CH:42]=N[CH:40]=[CH:39]2)=[O:37])C=1.[Cl:43][C:44]1[CH:45]=[C:46]([C@@H:50]([C@@H:59]2CCCN[CH2:60]2)[O:51][CH2:52][CH2:53][NH:54][C:55](=[O:58])[O:56][CH3:57])[CH:47]=[CH:48][CH:49]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:43][C:44]1[CH:45]=[C:46]([C@@H:50]([C@@H:59]2[CH2:60][CH2:40][CH2:39][N:38]([C:36](=[O:37])[NH:1][C@@H:2]([CH2:15][C@H:16]3[CH2:21][CH2:20][CH2:19][O:18][CH2:17]3)[CH2:3][N:4]([C:5]([O:6][CH2:7][CH2:8][Si:9]([CH3:12])([CH3:11])[CH3:10])=[O:13])[CH3:14])[CH2:42]2)[O:51][CH2:52][CH2:53][NH:54][C:55](=[O:58])[O:56][CH3:57])[CH:47]=[CH:48][CH:49]=1
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HCID 6422Trifluoroacetic acidHCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 580174332-(trimethylsilyl)ethyl (S)-2-amino-3-((R)-tetrahydro-2H-pyran-3-yl)propyl(methyl)carbamateHCID 59598478Carbamic acid,N-[2-[(R)-(3-chlorophenyl)(3R)-3-piperidinylmethoxy]ethyl]-,methyl ester

생성물 1

HCID 67363897
methyl 2-((R)-(3-chlorophenyl)((R)-1-((S)-1-(N-Methyl-2-(trimethylsilyl)ethoxycarbonylamino)-3-((R)-tetrahydro-2H-pyran-3-yl)propan-2-ylcarbamoyl)piperidin-3-yl)methoxy)ethylcarbamate
수율 75%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

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온도
0 °C

실험 절차

At 0° C., to a solution of 2-(trimethylsilyl)ethyl (S)-2-amino-3-((R)-tetrahydro-2H-pyran-3-yl)propyl(methyl)carbamate (1.9 g, 6 mmol) and DIPEA (3.87 g, 30 mmol) in anhydrous CH2Cl2 (20 mL) was added CDI (1.26 g, 7.8 mmol). After addition, the mixture was stirred for 1 hr at 0° C., followed by addition of methyl 2-((R)-(3-chlorophenyl)((R)-piperidin-3-yl)methoxy)ethylcarbamate as TFA salt (2.8 g, 6.6 mmol) in anhydrous CH2Cl2 (20 mL). The reaction mixture was allowed to warm to rt and stirred overnight. After the reaction was completed, the solvent was removed in vacuo. The product was purified by column chromatography on silica gel eluting with petroleum ether/EtOAc (5:1→2:1) to afford methyl 2-((R)-(3-chlorophenyl)((R)-1-((S)-1-(N-Methyl-2-(trimethylsilyl)ethoxycarbonylamino)-3-((R)-tetrahydro-2H-pyran-3-yl)propan-2-ylcarbamoyl)piperidin-3-yl)methoxy)ethylcarbamate (3.0 g, 75% yield).

후처리

  1. additionAfter addition
  2. temperatureto warm to rt
  3. stirringstirred overnight
  4. customthe solvent was removed in vacuo
  5. customThe product was purified by column chromatography on silica gel eluting with petroleum ether/EtOAc (5:1→2:1)

출처 및 근거

ORD 기록
ord-f398c4f705944c6ba50f2a3fdcfa6927
출처 데이터셋
uspto-grants-2013_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08487108B2

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