1-Hydroxybenzotriazole → 2-[3-fluoro-4-(methylsulfanyl)phenyl]-N-methoxy-N-methyl-3-(tetrahydro-2H-pyran-4-yl)propanamide

HRID 1881920Notes

Reaction equation

HRID 1881920 reaction equation
Cl.[CH3:2][O:3][NH:4][CH3:5].[F:6][C:7]1[CH:8]=[C:9]([CH:15]([CH2:19][CH:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)[C:16]([OH:18])=O)[CH:10]=[CH:11][C:12]=1[S:13][CH3:14].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>C(#N)C.C(OCC)(=O)C.C(N(CC)CC)C>[F:6][C:7]1[CH:8]=[C:9]([CH:15]([CH2:19][CH:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)[C:16]([N:4]([O:3][CH3:2])[CH3:5])=[O:18])[CH:10]=[CH:11][C:12]=1[S:13][CH3:14]

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 210939502-[3-fluoro-4-(methylsulfanyl)phenyl]-3-(tetrahydro-2H-pyran-4-yl)propanoic acid

Product 1

HCID 593316112-[3-fluoro-4-(methylsulfanyl)phenyl]-N-methoxy-N-methyl-3-(tetrahydro-2H-pyran-4-yl)propanamideYield 89.4%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of N-methoxymethanamine hydrochloride (467 mg) in acetonitrile (16 mL) was neutralized with triethylamine (1.82 mL), and 2-[3-fluoro-4-(methylsulfanyl)phenyl]-3-(tetrahydro-2H-pyran-4-yl)propanoic acid (1.30 g), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (918 mg) and 1-hydroxybenzotriazole (73.4 mg) were added under ice-cooling. The reaction mixture was warmed to room temperature and stirred overnight. The reaction mixture was diluted with ethyl acetate, and washed with water and saturated aqueous sodium hydrogen carbonate. The ethyl acetate layer was dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography, and the title compound (1.33 g, yield 89%) was obtained as a colorless amorphous solid from a fraction eluted with ethyl acetate-hexane (9:1, volume ratio).

Workup

  1. additionwere added under ice-
  2. temperaturecooling
  3. washwashed with water and saturated aqueous sodium hydrogen carbonate
  4. dry with materialThe ethyl acetate layer was dried (MgSO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-2ef2f4a6c70b4e2fa14339211f575116
Source dataset
uspto-grants-2012_11
Patent number
US08318746B2

Reaction notes

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