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

HRID 1881920노트

반응식

HRID 1881920 반응식
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]

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 6342Acetonitrile용매HCID 8471Triethylamine용매HCID 8857Ethyl Acetate용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-2ef2f4a6c70b4e2fa14339211f575116
출처 데이터셋
uspto-grants-2012_11
특허 번호
US08318746B2

반응 노트

불러오는 중…