Diisopropylethylamine → 2-(trimethylsilyl)ethyl (2S,3S)-3-((R)-3-((S)-1-(3-chloro-2-fluorophenyl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxamido)-4-cyclohexyl-2-hydroxybutylcarbamate

HRID 253596

反応式

HRID 253596 の反応式
[Cl:1][C:2]1[C:3]([F:22])=[C:4]([C@:8]([C@@H:16]2[CH2:21][CH2:20][CH2:19][NH:18][CH2:17]2)([OH:15])[CH2:9][CH2:10][CH2:11][CH2:12][O:13][CH3:14])[CH:5]=[CH:6][CH:7]=1.CCN(C(C)C)C(C)C.[N+](C1C=CC([O:39][C:40]([NH:42][C@@H:43]([CH2:61][CH:62]2[CH2:67][CH2:66][CH2:65][CH2:64][CH2:63]2)[C@@H:44]([O:56][Si](C)(C)C)[CH2:45][NH:46][C:47](=[O:55])[O:48][CH2:49][CH2:50][Si:51]([CH3:54])([CH3:53])[CH3:52])=O)=CC=1)([O-])=O>C(Cl)Cl>[Cl:1][C:2]1[C:3]([F:22])=[C:4]([C@:8]([C@@H:16]2[CH2:21][CH2:20][CH2:19][N:18]([C:40]([NH:42][C@@H:43]([CH2:61][CH:62]3[CH2:63][CH2:64][CH2:65][CH2:66][CH2:67]3)[C@@H:44]([OH:56])[CH2:45][NH:46][C:47](=[O:55])[O:48][CH2:49][CH2:50][Si:51]([CH3:52])([CH3:54])[CH3:53])=[O:39])[CH2:17]2)([OH:15])[CH2:9][CH2:10][CH2:11][CH2:12][O:13][CH3:14])[CH:5]=[CH:6][CH:7]=1

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 577864902-(trimethylsilyl)ethyl (2S,3S)-3-(4-nitrophenoxycarbonylamino)-4-cyclohexyl-2-(trimethylsilyloxy)butylcarbamateHCID 59382881(S)-1-(3-chloro-2-fluorophenyl)-5-methoxy-1-((R)-piperidin-3-yl)pentan-1-ol

生成物 1

HCID 577864752-(trimethylsilyl)ethyl (2S,3S)-3-((R)-3-((S)-1-(3-chloro-2-fluorophenyl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxamido)-4-cyclohexyl-2-hydroxybutylcarbamate収率 38%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

To a solution of (S)-1-(3-chloro-2-fluorophenyl)-5-methoxy-1-((R)-piperidin-3-yl)pentan-1-ol (33.0 mg, 0.10 mmol) in CH2Cl2 (2 mL), DIEA (39 mg, 0.30 mmol) was added, followed by the solution of 2-(trimethylsilyl)ethyl (2S,3S)-3-(4-nitrophenoxycarbonylamino)-4-cyclohexyl-2-(trimethylsilyloxy)butylcarbamate in CH2Cl2 (0.8 mL, 0.2 mmol) prepared in the previous step. The resulting yellow solution was stirred at rt for 30 min, and completion of reaction was confirmed by LC-MS. Solvent was removed under vacuum, and the residue was purified by preparative HPLC to give 2-(trimethylsilyl)ethyl (2S,3S)-3-((R)-3-((S)-1-(3-chloro-2-fluorophenyl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxamido)-4-cyclohexyl-2-hydroxybutylcarbamate (25.8 mg, 38%); MS m/z 686 (M+H+).

後処理

  1. customprepared in the previous step
  2. customcompletion of reaction
  3. customSolvent was removed under vacuum
  4. customthe residue was purified by preparative HPLC

出典と根拠

ORDレコード
ord-70e2bb168aef416589a2bb20822f0282
出典データセット
uspto-grants-2011_01
特許番号
US07872028B2

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