3-Methylthiopropionate → HCID 57669935, compound

HRID 1894488Notes

Reaction equation

HRID 1894488 reaction equation
[CH3:1][S:2][CH2:3][CH2:4][C:5]([OH:7])=O.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[C:27]([C:31]1[N:36]=[CH:35][C:34]([C:37]2[N:38]([C:58]([N:60]3[CH2:65][CH2:64][NH:63][CH2:62][CH2:61]3)=[O:59])[C@@:39]([C:51]3[CH:56]=[CH:55][C:54]([Cl:57])=[CH:53][CH:52]=3)([CH3:50])[C@@:40]([C:43]3[CH:48]=[CH:47][C:46]([Cl:49])=[CH:45][CH:44]=3)([CH3:42])[N:41]=2)=[C:33]([O:66][CH2:67][CH3:68])[CH:32]=1)([CH3:30])([CH3:29])[CH3:28]>CN(C)C=O>[C:27]([C:31]1[N:36]=[CH:35][C:34]([C:37]2[N:38]([C:58]([N:60]3[CH2:65][CH2:64][N:63]([C:5](=[O:7])[CH2:4][CH2:3][S:2][CH3:1])[CH2:62][CH2:61]3)=[O:59])[C@@:39]([C:51]3[CH:56]=[CH:55][C:54]([Cl:57])=[CH:53][CH:52]=3)([CH3:50])[C@@:40]([C:43]3[CH:44]=[CH:45][C:46]([Cl:49])=[CH:47][CH:48]=3)([CH3:42])[N:41]=2)=[C:33]([O:66][CH2:67][CH3:68])[CH:32]=1)([CH3:28])([CH3:29])[CH3:30]

Participants

6

Reactant 4

HCID 5633-MethylthiopropionateHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 57669930HCID 57669930, compound

Product 1

HCID 57669935HCID 57669935, compoundYield 89.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-(methylthio)propionic acid (30.8 mg, 0.256 mmole, Lancaster) in dimethylformamide (10 mL) were added successively 1-hydroxybenzotriazole (46.3 mg, 0.342 mmole, Chem-Impex), N,N,N′,N′-tetramethyl-O-(1H-Benzotriazol-1-yl)uranium hexafluorophosphate (130.0 mg, 0.343 mmole, Aldrich) and diisopropylethylamine (111.0 mg, 0.857 mmole). The mixture was stirred for 15 min before [(4S,5R)-2-(6-tert-butyl-4-ethoxy-pyridin-3-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-piperazin-1-yl-methanone (104.4 mg, 0.171 mmole) was added. The reaction mixture was allowed to stir for 1 h before concentrated under reduced pressure. The residue was dissolved in ethyl acetate and washed with 1 N sodium hydroxide, brine, dried and concentrated. The crude residue was purified by flash column chromatography (silica gel, eluting with a gradient of 1-10% methanol in methylene chloride) to give the title compound (108.7 mg, 89% yield). HR-MS (ES, m/z) calculated for C37H46Cl2N5O3S [(M+H)+] 710.2693, observed 710.2691.

Workup

  1. additionwas added
  2. concentrationbefore concentrated under reduced pressure
  3. dissolutionThe residue was dissolved in ethyl acetate
  4. washwashed with 1 N sodium hydroxide, brine
  5. customdried
  6. concentrationconcentrated
  7. customThe crude residue was purified by flash column chromatography (silica gel
  8. washeluting with a gradient of 1-10% methanol in methylene chloride)

Sources & evidence

ORD record
ord-9591cc40a51c443f8bff7a2365aef510
Source dataset
uspto-grants-2013_08
Patent number
US08513239B2

Reaction notes

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