Morpholine → HCID 178522098, compound

HRID 491767Notes

Reaction equation

HRID 491767 reaction equation
[C:1]([C:4]1[CH:5]=[CH:6][C:7]2[O:11][C:10]([C:12]([NH:14][C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][N:16]=3)=[O:13])=[C:9]([NH:22][C:23]([C@H:25]3[CH2:30][CH2:29][C@H:28]([N:31]4[CH2:35][CH2:34][CH2:33][C:32]4=[O:36])[CH2:27][CH2:26]3)=[O:24])[C:8]=2[CH:37]=1)(O)=[O:2].[NH:38]1[CH2:43][CH2:42][O:41][CH2:40][CH2:39]1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O.N1C=CC=CC=1>[N:38]1([C:1]([C:4]2[CH:5]=[CH:6][C:7]3[O:11][C:10]([C:12]([NH:14][C:15]4[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][N:16]=4)=[O:13])=[C:9]([NH:22][C:23]([C@H:25]4[CH2:26][CH2:27][C@H:28]([N:31]5[CH2:35][CH2:34][CH2:33][C:32]5=[O:36])[CH2:29][CH2:30]4)=[O:24])[C:8]=3[CH:37]=2)=[O:2])[CH2:43][CH2:42][O:41][CH2:40][CH2:39]1

Participants

6

Reactant 4

HCID 8083MorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 178524190HCID 178524190, compound

Product 1

HCID 178522098HCID 178522098, compoundYield 85.7%

Reagents, catalysts & solvents 1

HCID 21954950Dimethylformamide pyridineSolvent

Procedure

Trans-5-carboxy-3-[4-(2-oxopyrrolidin-1-yl)cyclohexylcarbonylamino]-N-(5-chloropyridin-2-yl)benzofuran-2-carboxamide (830 mg) obtained in Example 77 is suspended in N,N-dimethylformamide-pyridine (1:1, 30 ml), and thereto are added successively morpholine (196 mg), 1-hydroxybenzotriazole (406 mg) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (576 mg) under ice-cooling, and the mixture is stirred at room temperature for 17 hours. To the reaction solution are poured ice-water and a saturated aqueous sodium hydrogen carbonate solution, and the mixture is extracted with ethyl acetate, washed with water and a saturated brine, and dried over sodium sulfate. The solvent is evaporated under reduced pressure, and the resulting residue is purified by NH-silica gel column chromatography (eluent: chloroform). The resulting residue is suspended in ethyl acetate-n-hexane, and the precipitates are collected by filtration, and dried to give the title compound (805 mg).

Workup

  1. temperaturecooling
  2. extractiona saturated aqueous sodium hydrogen carbonate solution, and the mixture is extracted with ethyl acetate
  3. washwashed with water
  4. dry with materiala saturated brine, and dried over sodium sulfate
  5. customThe solvent is evaporated under reduced pressure
  6. customthe resulting residue is purified by NH-silica gel column chromatography (eluent: chloroform)
  7. filtrationthe precipitates are collected by filtration
  8. customdried

Sources & evidence

ORD record
ord-0fb146b3b11243489bda74fedab5caac
Source dataset
uspto-grants-2009_05
Patent number
US07531537B2

Reaction notes

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