Citric Acid → N-methoxy-N-methyl-2-[1-methyl-5-(methylsulfanyl)-1H-pyrazol-3-yl]-3-(tetrahydro-2H-pyran-4-yl)propanamide

HRID 1802879Notes

Reaction equation

HRID 1802879 reaction equation
[CH3:1][N:2]1[C:6]([S:7][CH3:8])=[CH:5][C:4]([CH:9]([CH2:13][CH:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[C:10]([OH:12])=O)=[N:3]1.Cl.[CH3:21][O:22][NH:23][CH3:24].N1(O)C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C)C=O.C(N(CC)CC)C>[CH3:21][O:22][N:23]([CH3:24])[C:10](=[O:12])[CH:9]([C:4]1[CH:5]=[C:6]([S:7][CH3:8])[N:2]([CH3:1])[N:3]=1)[CH2:13][CH:14]1[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1

Participants

8

Reactant 5

HCID 311Citric AcidHCID 757711-HydroxybenzotriazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 583806222-[1-methyl-5-(methylsulfanyl)-1H-pyrazol-3-yl]-3-(tetrahydro-2H-pyran-4-yl)propanoic acid

Product 1

HCID 58380601N-methoxy-N-methyl-2-[1-methyl-5-(methylsulfanyl)-1H-pyrazol-3-yl]-3-(tetrahydro-2H-pyran-4-yl)propanamideYield 63.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a mixture of 2-[1-methyl-5-(methylsulfanyl)-1H-pyrazol-3-yl]-3-(tetrahydro-2H-pyran-4-yl)propanoic acid (1.09 g), N-methoxymethanamine hydrochloride (0.75 g), 1H-1,2,3-benzotriazol-1-ol (0.70 g), triethylamine (1.1 mL) and N,N-dimethylformamide (10 mL) was added N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (0.88 g) at 0° C., and the mixture was stirred overnight at room temperature. To the reaction mixture was added 10% aqueous citric acid solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed successively with saturated brine, saturated aqueous sodium hydrogen carbonate and saturated brine, dried (MgSO1), and concentrated. The obtained residue was subjected to silica gel column chromatography to give the title compound (0.80 g, yield 63%) as a colorless oil from the fraction eluted with ethyl acetate-hexane (4:1, volume ratio). MS: 328 (MH+).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe ethyl acetate layer was washed successively with saturated brine, saturated aqueous sodium hydrogen carbonate and saturated brine
  3. customdried (MgSO1)
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-19cb69d2d69c40359194db768db80e1e
Source dataset
uspto-grants-2013_01
Patent number
US08349886B2

Reaction notes

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