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

HRID 73874Notes

Reaction equation

HRID 73874 reaction equation
C(N(CC)C(C)C)(C)C.[CH3:10][N:11]1[CH2:16][CH2:15][N:14]([C:17]2[S:18][CH:19]=[C:20]([C:22]3[CH:27]=[CH:26][C:25]([C:28]([NH:30][C:31]4([C:37]([NH:39][C@H:40]([CH2:45][OH:46])[CH2:41][CH2:42][S:43][CH3:44])=[O:38])[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]4)=[O:29])=[CH:24][CH:23]=3)[N:21]=2)[CH2:13][CH2:12]1>CS(C)=O.C(Cl)Cl>[CH3:10][N:11]1[CH2:16][CH2:15][N:14]([C:17]2[S:18][CH:19]=[C:20]([C:22]3[CH:23]=[CH:24][C:25]([C:28]([NH:30][C:31]4([C:37]([NH:39][C@H:40]([CH:45]=[O:46])[CH2:41][CH2:42][S:43][CH3:44])=[O:38])[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]4)=[O:29])=[CH:26][CH:27]=3)[N:21]=2)[CH2:13][CH2:12]1

Participants

5

Reactant 2

HCID 81531DiisopropylethylamineHCID 57672850N-[[1-[[[4-[2-(4-Methyl-1-piperazinyl)-4-thiazolyl]phenyl]carbonyl]amino]cyclohexyl]carbonyl]-L-methioninol

Product 1

HCID 57672869N-[[1-[[[4-[2-(4-Methyl-1-piperazinyl)-4-thiazolyl]phenyl]carbonyl]amino]cyclohexyl]carbonyl]-L-methioninalYield 64.4%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 6344DichloromethaneSolvent

Procedure

Under an argon gas atmosphere, 453 mg (3.5 mmol) of N,N-diisopropylethylamine was added dropwise to a solution of 658 mg (3.5 mmol) of sulfur trioxide-pyridine complex in 10 ml of anhydrous dimethyl sulfoxide and 5 ml of anhydrous methylene chloride under ice-cooling, and the mixture was stirred for 15 minutes. Further, under ice-cooling, a solution of 319 mg (0.58 mmol) of N-[[1-[[[4-[2-(4-methyl-1-piperazinyl)-4-thiazolyl]phenyl]carbonyl]amino]cyclohexyl]carbonyl]-L-methioninol in 3 ml of anhydrous dimethyl sulfoxide was added to the reaction solution, and the mixture was stirred at the same temperature for 2 hours. The reaction solution was poured to ice-water and extracted with ethyl acetate twice. The organic layer was washed with a saturated aqueous sodium hydrogencarbonate solution and then saturated brine, and after it was dried with anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure. 20 ml of diisopropyl ether was added to the residue, and the mixture was stirred at room temperature for 18 hours. The obtained crystal was collected by filtration to obtain 203 mg (64%) of the title compound.

Workup

  1. temperaturecooling
  2. temperatureFurther, under ice-cooling
  3. stirringthe mixture was stirred at the same temperature for 2 hours
  4. extractionextracted with ethyl acetate twice
  5. washThe organic layer was washed with a saturated aqueous sodium hydrogencarbonate solution
  6. dry with materialsaturated brine, and after it was dried with anhydrous magnesium sulfate
  7. distillationthe solvent was distilled off under reduced pressure
  8. addition20 ml of diisopropyl ether was added to the residue
  9. stirringthe mixture was stirred at room temperature for 18 hours
  10. filtrationThe obtained crystal was collected by filtration

Sources & evidence

ORD record
ord-40b820917d6d4db4927a38bfc127e04e
Source dataset
uspto-grants-2014_09
Patent number
US08829209B2

Reaction notes

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