Triethylamine → 4-(4-Bromo-2-fluorophenyl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

HRID 533521노트

반응식

HRID 533521 반응식
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([S:15]([CH3:18])(=[O:17])=[O:16])([CH3:14])[C:11]([OH:13])=O)=[C:4]([F:19])[CH:3]=1.[O:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH:21]1[O:26][NH2:27].O.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.Cl.CN(C)CCCN=C=NCC>ClCCl.O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([CH3:14])([S:15]([CH3:18])(=[O:17])=[O:16])[C:11]([NH:27][O:26][CH:21]2[CH2:22][CH2:23][CH2:24][CH2:25][O:20]2)=[O:13])=[C:4]([F:19])[CH:3]=1

참가 물질

8

반응물 5

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 665779184-(4-Bromo-2-fluoro-phenyl)-2-methanesulfonyl-2-methyl-butyric acid

생성물 1

HCID 866687574-(4-Bromo-2-fluorophenyl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide수율 79.9%

시약·촉매·용매 2

HCID 962Water용매HCID 6344Dichloromethane용매2회

실험 절차

4-(4-Bromo-2-fluoro-phenyl)-2-methanesulfonyl-2-methyl-butyric acid (1.96 g, 5.55 mmol), O-tetrahydro-2H-pyran-2-yl-hydroxylamine (0.910 g, 7.77 mmol), 1-hydroxy benzotriazole monohydrate (1.53 g, 9.99 mmol), triethylamine (1.39 mL, 9.99 mmol) and 1, (3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.49 g, 7.77 mmol) were combined followed by the addition 60 mL of dichloromethane. The reaction was allowed to stir at room temperature overnight, was then diluted with 20 mL of dichloromethane and 60 mL of water. The aqueous layer was re-extracted with DCM (2×40 mL). The organics were combined, dried over magnesium sulfate, filtered and concentrated onto silica gel. Silica chromatography (40% ethyl acetate 60% heptane to 40% ethyl acetate 60% heptane to 80% ethyl acetate 20% heptane for 60 minutes) afforded the title compound as a white foam 2.0 g, (79.9%). LC-MS m/z 452.1 (M−1)

후처리

  1. extractionThe aqueous layer was re-extracted with DCM (2×40 mL)
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated onto silica gel

출처 및 근거

ORD 기록
ord-185b4f59ea054aeebe04b06c8fa276f7
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08853258B2

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