1-Hydroxybenzotriazole → 1-[[[4-[2-(4-Methyl-1-piperazinyl)-4-thiazolyl]phenyl]carbonyl]amino]cyclohexanecarboxylic acid phenylmethyl ester

HRID 73866Notes

Reaction equation

HRID 73866 reaction equation
Cl.C(N=C=NCCCN(C)C)C.Br.[CH3:14][N:15]1[CH2:20][CH2:19][N:18]([C:21]2[S:22][CH:23]=[C:24]([C:26]3[CH:34]=[CH:33][C:29]([C:30](O)=[O:31])=[CH:28][CH:27]=3)[N:25]=2)[CH2:17][CH2:16]1.ON1C2C=CC=CC=2N=N1.[C:45]1([CH2:51][O:52][C:53]([C:55]2([NH2:61])[CH2:60][CH2:59][CH2:58][CH2:57][CH2:56]2)=[O:54])[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[C:45]1([CH2:51][O:52][C:53]([C:55]2([NH:61][C:30]([C:29]3[CH:33]=[CH:34][C:26]([C:24]4[N:25]=[C:21]([N:18]5[CH2:17][CH2:16][N:15]([CH3:14])[CH2:20][CH2:19]5)[S:22][CH:23]=4)=[CH:27][CH:28]=3)=[O:31])[CH2:56][CH2:57][CH2:58][CH2:59][CH2:60]2)=[O:54])[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=1

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 15176238Benzyl 1-aminocyclohexanecarboxylateHCID 669210514-[2-(4-Methyl-1-piperazinyl)-4-thiazolyl]benzoic acid hydrobromide

Product 1

HCID 576728201-[[[4-[2-(4-Methyl-1-piperazinyl)-4-thiazolyl]phenyl]carbonyl]amino]cyclohexanecarboxylic acid phenylmethyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Under ice-cooling, 5.29 g (374 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride was added to a solution of 8.84 g (23.0 mmol) of 4-[2-(4-methyl-1-piperazinyl)-4-thiazolyl]benzoic acid hydrobromide, 4.19 g (27.6 mmol) of 1-hydroxybenzotriazole, 6.44 g (27.6 mmol) of 1-aminocyclohexanecarboxylic acid phenylmethyl ester and 11.9 g (92 mmol) of N,N-diisopropylethylamine in 120 ml of dimethylformamide. After the mixture was stirred at room temperature overnight, 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, ether was added to the residue to wash the crystal to obtain 11.8 g (quantitative) of the title compound.

Workup

  1. temperatureUnder ice-cooling
  2. concentrationthe reaction solution was concentrated under reduced pressure, ethyl acetate
  3. additionwas added
  4. washthe mixture was successively washed with water
  5. dry with materialby drying with anhydrous sodium sulfate
  6. distillationAfter the solvent was distilled off under reduced pressure, ether
  7. additionwas added to the residue
  8. washto wash the crystal

Sources & evidence

ORD record
ord-db59aa1527d0471da4bd39b633a21239
Source dataset
uspto-grants-2014_09
Patent number
US08829209B2

Reaction notes

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