1-Hydroxybenzotriazole → HCID 68914192, compound

HRID 732728Notes

Reaction equation

HRID 732728 reaction equation
[CH2:1]([N:8]1[C:12](=[O:13])[CH2:11][CH:10]([C:14]([OH:16])=O)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.[CH3:39][C@@H:40]([NH2:51])[C:41]1[C:50]2[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=2)[CH:44]=[CH:43][CH:42]=1>O.CN(C=O)C>[CH2:1]([N:8]1[C:12](=[O:13])[CH2:11][C@@H:10]([C:14]([NH:51][C@@H:40]([C:41]2[C:50]3[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=3)[CH:44]=[CH:43][CH:42]=2)[CH3:39])=[O:16])[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 990241-Benzyl-5-oxo-pyrrolidine-3-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2724264(+)-1-(1-Naphthyl)ethylamine

Product 1

HCID 68914192HCID 68914192, compoundYield 42.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A 20 ml DMF solution of 1.16 g of 1-benzyl-5-oxopyrrolidine-3-carboxylic acid was mixed with 2.0 g of WSC hydrochloride and 859 mg of HOBt and stirred at room temperature for 30 minutes. 1.1 g of (1R)-1-naphthylethylamine was added thereto successively and stirred at 60° C. After completion of the reaction, this was mixed with 100 ml of water, extracted with ethyl acetate and washed with 1 M hydrochloric acid. The organic layer was concentrated, and the thus obtained residue was purified by a silica gel column chromatography (chloroform-methanol) and then recrystallized from ethyl acetate-hexane to obtain 856 mg and 831 mg of (3R)-1-benzyl-N-[(1R)-1-(1-naphthyl)ethyl]5-oxopyrrolidine-3-carboxamide and (3S)-1-benzyl-N-[(1R)-1-(1-naphthyl)ethyl]5-oxopyrrolidine-3-carboxamide (stereoisomers un-verified). Both of the thus obtained compounds were respectively subjected to reduction in the same manner as in Example 84, made into salt with fumaric acid and recrystallized from ethanol-ethyl acetate to obtain (1R)—N-{[(3S)-1-benzylpyrrolidin-3-yl]methyl}-1-(1-naphthyl)ethanamine fumarate and (1R)—N-{[(3R)-1-benzylpyrrolidin-3-yl]methyl}-1-(1-naphthyl)ethanamine fumarate.

Workup

  1. stirringsuccessively and stirred at 60° C
  2. customAfter completion of the reaction
  3. extractionextracted with ethyl acetate
  4. washwashed with 1 M hydrochloric acid
  5. concentrationThe organic layer was concentrated
  6. customthe thus obtained residue was purified by a silica gel column chromatography (chloroform-methanol)
  7. customrecrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-c12ef7f7e4e54ccf9d54fc972d5f1e55
Source dataset
uspto-grants-2009_09
Patent number
US07585886B2

Reaction notes

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