Diisopropylethylamine → N-[[1-[[[4-[2-(4-Methyl-1-piperazinyl)-4-thiazolyl]phenyl]carbonyl]amino]cyclohexyl]carbonyl]-L-methionine methyl ester

HRID 1627495Notes

Reaction equation

HRID 1627495 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:11])[C@H:5]([CH2:7][CH2:8][S:9][CH3:10])[NH2:6].[CH3:12][N:13]1[CH2:18][CH2:17][N:16]([C:19]2[S:20][CH:21]=[C:22]([C:24]3[CH:29]=[CH:28][C:27]([C:30]4[O:34][C:33](=[O:35])[C:32]5([CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]5)[N:31]=4)=[CH:26][CH:25]=3)[N:23]=2)[CH2:15][CH2:14]1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[CH3:2][O:3][C:4](=[O:11])[C@H:5]([CH2:7][CH2:8][S:9][CH3:10])[NH:6][C:33]([C:32]1([NH:31][C:30]([C:27]2[CH:28]=[CH:29][C:24]([C:22]3[N:23]=[C:19]([N:16]4[CH2:15][CH2:14][N:13]([CH3:12])[CH2:18][CH2:17]4)[S:20][CH:21]=3)=[CH:25][CH:26]=2)=[O:34])[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40]1)=[O:35]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 11435579L-Methionine, methyl ester, hydrochlorideHCID 576728032-[4-[2-(4-Methyl-1-piperazinyl)-4-thiazolyl]phenyl]-3-oxa-1-azaspiro[4.5]dec-1-en-4-one

Product 1

HCID 57672925N-[[1-[[[4-[2-(4-Methyl-1-piperazinyl)-4-thiazolyl]phenyl]carbonyl]amino]cyclohexyl]carbonyl]-L-methionine methyl esterYield 33.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

200 mg (1.00 mmol) of L-methionine methyl ester hydrochloride was added to a solution of 411 mg (1.00 mmol) of 2-[4-[2-(4-methyl-1-piperazinyl)-4-thiazolyl]phenyl]-3-oxa-1-azaspiro[4.5]dec-1-en-4-one and 258 mg (2.00 mmol) of N,N-diisopropylethylamine in 20 ml of dimethylformamide. After the mixture was stirred at 80° C. for 15 hours, the reaction solution was concentrated under reduced pressure, ethyl acetate was added thereto, and the mixture was successively washed with water, a saturated aqueous sodium hydrogencarbonate solution and saturated brine, followed by drying with anhydrous sodium sulfate. After the solvent was distilled off under reduced pressure, the residue was purified by silica gel chromatography to obtain 191 mg (33%) of the title compound.

Workup

  1. concentrationthe reaction solution was concentrated under reduced pressure, ethyl acetate
  2. additionwas added
  3. washthe mixture was successively washed with water
  4. dry with materialby drying with anhydrous sodium sulfate
  5. distillationAfter the solvent was distilled off under reduced pressure
  6. customthe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-bd196cdf492b42ab810d1d7d20396218
Source dataset
uspto-grants-2014_07
Patent number
US08785631B2

Reaction notes

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