Methyl chloroformate → 2-(trimethylsilyl)ethyl (S)-2-((R)-3-((R)-(2-(methoxycarbonylamino)propoxy)(3-chlorophenyl)methyl)piperidine-1-carboxamido)-3-cyclohexylpropyl(methyl)carbamate

HRID 451920Notes

Reaction equation

HRID 451920 reaction equation
[NH2:1][CH:2]([CH3:42])[CH2:3][O:4][C@@H:5]([C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([Cl:41])[CH:36]=1)[C@@H:6]1[CH2:11][CH2:10][CH2:9][N:8]([C:12]([NH:14][C@@H:15]([CH2:28][CH:29]2[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]2)[CH2:16][N:17]([CH3:27])[C:18](=[O:26])[O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])=[O:13])[CH2:7]1.CCN(C(C)C)C(C)C.Cl[C:53]([O:55][CH3:56])=[O:54]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH3:56][O:55][C:53]([NH:1][CH:2]([CH3:42])[CH2:3][O:4][C@@H:5]([C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([Cl:41])[CH:36]=1)[C@@H:6]1[CH2:11][CH2:10][CH2:9][N:8]([C:12]([NH:14][C@@H:15]([CH2:28][CH:29]2[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34]2)[CH2:16][N:17]([CH3:27])[C:18](=[O:26])[O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])=[O:13])[CH2:7]1)=[O:54]

Participants

6

Reactant 3

HCID 6586Methyl chloroformateHCID 81531DiisopropylethylamineHCID 866394612-(trimethylsilyl)ethyl (2S)-2-((3R)-3-((1R)-(2-aminopropoxy)(3-chlorophenyl)methyl)piperidine-1-carboxamido)-3-cyclohexylpropyl(methyl)carbamate

Product 1

HCID 866394622-(trimethylsilyl)ethyl (S)-2-((R)-3-((R)-(2-(methoxycarbonylamino)propoxy)(3-chlorophenyl)methyl)piperidine-1-carboxamido)-3-cyclohexylpropyl(methyl)carbamate

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of crude 2-(trimethylsilyl)ethyl (2S)-2-((3R)-3-((1R)-(2-aminopropoxy)(3-chlorophenyl)methyl)piperidine-1-carboxamido)-3-cyclohexylpropyl(methyl)carbamate (0.1340 g), obtained as, described above, DMAP (0.151 g), DIPEA (2 mL), and methyl chloroformate (0.483 g) in CH2Cl2 was stirred at rt for 2 d. After the reaction mixture was evaporated under reduced pressure, the crude product was purified by reversed-phase HPLC to give 2-(trimethylsilyl)ethyl (S)-2-((R)-3-((R)-(2-(methoxycarbonylamino)propoxy)(3-chlorophenyl)methyl)piperidine-1-carboxamido)-3-cyclohexylpropyl(methyl)carbamate. MS ESI +ve m/z 705 (M+Na).

Workup

  1. customobtained as,
  2. customAfter the reaction mixture was evaporated under reduced pressure
  3. customthe crude product was purified by reversed-phase HPLC

Sources & evidence

ORD record
ord-ea51a4d5993a46a79a0af1d781b69404
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Reaction notes

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