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

HRID 2355488ノート

反応式

HRID 2355488 の反応式
[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.[Si](Cl)(C)(C)C.Cl[C:29](OC1C=CC([N+]([O-])=O)=CC=1)=[O:30].Cl.[Cl: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>[Cl: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

参加物

7

反応物 4

HCID 6397ChlorotrimethylsilaneHCID 821294-Nitrophenyl chloroformateHCID 67189342HCID 67189342、化合物HCID 67191599(S)-1-(3-chlorophenyl)-5-methoxy-1-((R)-piperidin-3-yl)pentan-1-ol hydrochloride

生成物 1

HCID 67190261(3R)-3-((S)-1-(3-chlorophenyl)-1-hydroxy-5-methoxypentyl)-N-(3-(1-hydroxycyclohexyl)-1-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)propan-2-yl)piperidine-1-carboxamide収率 54.4%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8471Triethylamine溶媒

実験手順

To a solution of (2-(trimethylsilyl)ethyl 3-(1-hydroxycyclohexyl)-2-aminopropylmethylcarbamate (18.3 mg, 0.055 mmol) in CH2Cl2 (2 mL) were added Et3N (0.2 mL) and Me3SiCl (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), then pyridine (0.05 mL) was added, followed by 4-nitrophenyl chloroformate (13.5 mg, 0.66 mmol). The mixture was stirred for 30 min and (S)-1-(3-chlorophenyl)-5-methoxy-1-((R)-piperidin-3-yl)pentan-1-ol hydrochloride (19 mg, 0.055 mmol) was added. The mixture was stirred for 10 min and evaporated. The residue was purified by prep HPLC to give (3R)-3-((S)-1-(3-chlorophenyl)-1-hydroxy-5-methoxypentyl)-N-(3-(1-hydroxycyclohexyl)-1-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)propan-2-yl)piperidine-1-carboxamide (20 mg, 54%). MS m/z 668 (M+H+).

後処理

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

出典と根拠

ORDレコード
ord-1913184e6f87481eb467e9638d15a493
出典データセット
uspto-grants-2010_07
特許番号
US07754737B2

反応ノート

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