4-Methylmorpholine → 2-Acetyl-N-{1-[3-(4-methylbenzyl)-5-oxo-4,5-dihydro-1,2,4-triazin-6-yl]ethyl}-hexanamide

HRID 890705Notes

Reaction equation

HRID 890705 reaction equation
ON1C2C=CC=CC=2N=N1.CN1CCOCC1.Cl.CN(C)CCCN=C=NCC.[NH2:30][CH:31]([C:33]1[C:34](=[O:47])[NH:35][C:36]([CH2:39][C:40]2[CH:45]=[CH:44][C:43]([CH3:46])=[CH:42][CH:41]=2)=[N:37][N:38]=1)[CH3:32].[C:48]([CH:51]([CH2:55][CH2:56][CH2:57][CH3:58])[C:52](O)=[O:53])(=[O:50])[CH3:49]>>[C:48]([CH:51]([CH2:55][CH2:56][CH2:57][CH3:58])[C:52]([NH:30][CH:31]([C:33]1[C:34](=[O:47])[NH:35][C:36]([CH2:39][C:40]2[CH:45]=[CH:44][C:43]([CH3:46])=[CH:42][CH:41]=2)=[N:37][N:38]=1)[CH3:32])=[O:53])(=[O:50])[CH3:49]

Participants

6

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 193527442-Acetylhexanoic Acid2×HCID 1356979156-(1-Aminoethyl)-3-(4-methylbenzyl)-1,2,4-triazin-5(4H)-one

Product 1

HCID 1354945642-Acetyl-N-{1-[3-(4-methylbenzyl)-5-oxo-4,5-dihydro-1,2,4-triazin-6-yl]ethyl}-hexanamide

Conditions

Temperature
-20 °C

Procedure

The amount of 2-acetylhexanoic acid in dichloromethane from Example 15A is treated with 2.3 g (17.0 mmol) of 1-hydroxy-1H-benzotriazole and 3.44 g (34 mmol) of 4-methylmorpholine and cooled to −20° C. After addition of 3.26 g (17.0 mmol) of N′-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride, the mixture is stirred for 30 min. The cooling bath is removed in the course of this. 1.60 g (6.55 mmol) of 6-(1-aminoethyl)-3-(4-methylbenzyl)-1,2,4-triazin-5(4H)-one (Example 8A) are then added after fresh cooling to −20° C. and the mixture is stirred overnight while warming to room temperature. For work-up, the dichloromethane phase is washed with 1 N potassium hydrogensulphate solution and then with saturated sodium hydrogencarbonate solution. The dried organic phase is concentrated and chromatographed using the eluent dichloromethane/methanol 100/1 to 30/1.

Workup

  1. customThe cooling bath is removed in the course of this
  2. temperatureafter fresh cooling to −20° C.
  3. stirringthe mixture is stirred overnight
  4. temperaturewhile warming to room temperature
  5. washFor work-up, the dichloromethane phase is washed with 1 N potassium hydrogensulphate solution
  6. concentrationThe dried organic phase is concentrated
  7. customchromatographed

Sources & evidence

ORD record
ord-9720964236f34f5abf5201b1cf188a9f
Source dataset
uspto-grants-2006_02
Patent number
US06998402B2

Reaction notes

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