Chlorotrimethylsilane → (3R)-3-((S)-1-(3-fluorophenyl)-1-hydroxy-5-methoxypentyl)-N-(3-(1-hydroxycyclohexyl)-1-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)propan-2-yl)piperidine-1-carboxamide

HRID 1254371노트

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HRID 1254371 반응식
[OH:1][C:2]1([CH2:8][CH:9]([NH2:22])[CH2:10][N:11]([CH3:21])[C:12](=[O:20])[O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.C[Si](Cl)(C)C.Cl[C:29](OC1C=CC([N+]([O-])=O)=CC=1)=[O:30].Cl.[F:42][C:43]1[CH:44]=[C:45]([C@:49]([C@@H:57]2[CH2:62][CH2:61][CH2:60][NH:59][CH2:58]2)([OH:56])[CH2:50][CH2:51][CH2:52][CH2:53][O:54][CH3:55])[CH:46]=[CH:47][CH:48]=1>C(Cl)Cl.CCN(CC)CC>[F:42][C:43]1[CH:44]=[C:45]([C@:49]([C@@H:57]2[CH2:62][CH2:61][CH2:60][N:59]([C:29]([NH:22][CH:9]([CH2:8][C:2]3([OH:1])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]3)[CH2:10][N:11]([CH3:21])[C:12]([O:13][CH2:14][CH2:15][Si:16]([CH3:17])([CH3:19])[CH3:18])=[O:20])=[O:30])[CH2:58]2)([OH:56])[CH2:50][CH2:51][CH2:52][CH2:53][O:54][CH3:55])[CH:46]=[CH:47][CH:48]=1

참가 물질

7

반응물 4

HCID 6397ChlorotrimethylsilaneHCID 821294-Nitrophenyl chloroformateHCID 67189342HCID 67189342, 화합물HCID 67192771(S)-1-(3-fluorophenyl)-5-methoxy-1-((R)-piperidin-3-yl)pentan-1-ol hydrochloride

생성물 1

HCID 67189295(3R)-3-((S)-1-(3-fluorophenyl)-1-hydroxy-5-methoxypentyl)-N-(3-(1-hydroxycyclohexyl)-1-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)propan-2-yl)piperidine-1-carboxamide수율 50%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8471Triethylamine용매

실험 절차

To a solution of 2-(trimethylsilyl)ethyl 3-(1-hydroxycyclohexyl)-2-amino-propylmethylcarbamate (18.3 mg, 0.055 mmol) in CH2Cl2 (2 mL) was added Et3N (0.2 mL) and TMSCl (12 mg, 14 μL, 0.11 mmol). The resulting solution was stirred for 1 h and evaporated under vacuum. The residue was dissolved in CH2Cl2 (2 mL) and pyridine (0.05 mL) was added, followed by 4-nitrophenyl chloroformate (13.5 mg, 0.66 mmol). The solution was stirred for 30 min and (S)-1-(3-fluorophenyl)-5-methoxy-1-((R)-piperidin-3-yl)pentan-1-ol hydrochloride (18 mg, 0.055 mmol). The resulting mixture was stirred for 10 min and evaporated. The residue was purified by prep HPLC to give (3R)-3-((S)-1-(3-fluorophenyl)-1-hydroxy-5-methoxypentyl)-N-(3-(1-hydroxycyclohexyl)-1-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)propan-2-yl)piperidine-1-carboxamide (17.8 mg, 50%). MS m/z 652 (M+H+).

후처리

  1. customevaporated under vacuum
  2. dissolutionThe residue was dissolved in CH2Cl2 (2 mL)
  3. additionpyridine (0.05 mL) was added
  4. stirringThe solution was stirred for 30 min
  5. stirringThe resulting mixture was stirred for 10 min
  6. customevaporated
  7. customThe residue was purified by prep HPLC

출처 및 근거

ORD 기록
ord-40e17cfef3ff4d509d6bf42baaade0b8
출처 데이터셋
uspto-grants-2013_06
특허 번호
US08455521B2

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