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

HRID 1881814Notes

Reaction equation

HRID 1881814 reaction equation
Cl.[CH3:2][O:3][NH:4][CH3:5].[CH:6]1([S:9]([C:12]2[CH:17]=[CH:16][C:15]([CH:18]([CH2:22][CH:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)[C:19](O)=[O:20])=[CH:14][CH:13]=2)(=[O:11])=[O:10])[CH2:8][CH2:7]1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>CN(C)C=O.C(OCC)(=O)C.C(N(CC)CC)C>[CH:6]1([S:9]([C:12]2[CH:13]=[CH:14][C:15]([CH:18]([CH2:22][CH:23]3[CH2:24][CH2:25][O:26][CH2:27][CH2:28]3)[C:19]([N:4]([O:3][CH3:2])[CH3:5])=[O:20])=[CH:16][CH:17]=2)(=[O:10])=[O:11])[CH2:8][CH2:7]1

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 103150842-(4-(Cyclopropylsulfonyl)phenyl)-3-(tetrahydro-2H-pyran-4-YL)propanoic acid

Product 1

HCID 593315972-[4-(cyclopropylsulfonyl)phenyl]-N-methoxy-N-methyl-3-(tetrahydro-2H-pyran-4-yl)propanamideYield 81%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent2×HCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-methoxymethanamine hydrochloride (3.90 g) in N,N-dimethylformamide (100 mL) was added triethylamine (5.60 mL) for neutralization, and a solution of 2-[4-(cyclopropylsulfonyl)phenyl]-3-(tetrahydro-2H-pyran-4-yl)propanoic acid (11.23 g) in N,N-dimethylformamide (50 mL), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (9.60 g) and 1-hydroxybenzotriazole (6.80 g) 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, 1N aqueous hydrochloric acid solution 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 (10.2 g, yield 81%) was obtained as colorless amorphous crystals from a fraction eluted with ethyl acetate-hexane (1:1, volume ratio). MS: 382 (MH+).

Workup

  1. temperaturecooling
  2. washwashed with water, 1N aqueous hydrochloric acid solution and saturated aqueous sodium hydrogen carbonate
  3. dry with materialThe ethyl acetate layer was dried (MgSO4)
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-145306b2032c425ab589b4913a497362
Source dataset
uspto-grants-2012_11
Patent number
US08318746B2

Reaction notes

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