Toluene → N-((R)-1-((R)-2-amino-3-(1-(hydroxymethyl)cyclopropylamino)-3-oxopropylthio)-3-(hexadecyloxy)propan-2-yl)dodecanamide

HRID 2407874Notes

Reaction equation

HRID 2407874 reaction equation
[C:1]([NH:14][C@H:15]([CH2:46][O:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH2:62][CH3:63])[CH2:16][S:17][CH2:18][C@H:19]([NH:28]C(=O)OCC1C2C=CC=CC=2C2C1=CC=CC=2)[C:20]([NH:22][C:23]1([CH2:26][OH:27])[CH2:25][CH2:24]1)=[O:21])(=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].N1CCCCC1.C1(C)C=CC=CC=1>C(#N)C.C(Cl)Cl>[NH2:28][C@H:19]([C:20]([NH:22][C:23]1([CH2:26][OH:27])[CH2:25][CH2:24]1)=[O:21])[CH2:18][S:17][CH2:16][C@H:15]([NH:14][C:1](=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])[CH2:46][O:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH2:62][CH3:63]

Participants

6

Reactant 3

HCID 1140TolueneHCID 8082PiperidineHCID 86678277(9H-fluoren-9-yl)methyl (R)-3-((R)-2-dodecanamido-3-(hexadecyloxy)propylthio)-1-(1-(hydroxymethyl)cyclopropylamino)-1-oxopropan-2-ylcarbamate

Product 1

HCID 53476315N-((R)-1-((R)-2-amino-3-(1-(hydroxymethyl)cyclopropylamino)-3-oxopropylthio)-3-(hexadecyloxy)propan-2-yl)dodecanamide

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (9H-fluoren-9-yl)methyl (R)-3-((R)-2-dodecanamido-3-(hexadecyloxy) propylthio)-1-(1-(hydroxymethyl)cyclopropylamino)-1-oxopropan-2-ylcarbamate (1 eq) was added 20% piperidine (50 eq) in acetonitrile. The resulting gel was diluted with DCM and sonicated for 3 minutes. The mixture was added to toluene and then concentrated en vaccuo. The crude mixture was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 100% EtOAc then 0-10% MeOH/DCM to give N-((R)-1-((R)-2-amino-3-(1-(hydroxymethyl)cyclopropylamino)-3-oxopropylthio)-3-(hexadecyloxy)propan-2-yl)dodecanamide. 1H NMR (DMSO d-6): δ 8.13 (s, 2H), 7.73 (d, 2H), 4.68 (t, 2H), 3.89-3.97 (m, 2H), 3.35-3.44 (m, 5H), 3.20-3.24 (m, 1H), 2.59-2.74 (m, 4H), 2.32-2.34 (m, 1H), 2.05 (t, 2H), 1.42-1.50 (m, 4H), 1.21-1.28 (m, 40H), 0.85 (t, 6H), 0.67 (dd, 2H), 0.56 (dd, 2H). LRMS [M+H]=670.6.

Workup

  1. customsonicated for 3 minutes
  2. concentrationconcentrated en vaccuo
  3. customThe crude mixture was purified by flash chromatography on a COMBIFLASH® system (ISCO)

Sources & evidence

ORD record
ord-127bd66621b74334ada02cd97e564060
Source dataset
uspto-grants-2014_08
Patent number
US08808703B2

Reaction notes

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