4-Fluoro-1-naphthoic acid → 4-fluoro-N-{(1RS,2SR)-2-(2-fluoropyridin-4-yl)-2-hydroxy-1-[3-(1,1,2,2-tetrafluoroethoxy)benzyl]ethyl}-1-naphthamide

HRID 1610609노트

반응식

HRID 1610609 반응식
[NH2:1][CH:2]([CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([O:19][C:20]([F:25])([F:24])[CH:21]([F:23])[F:22])[CH:14]=1)[CH:3]([C:5]1[CH:10]=[CH:9][N:8]=[C:7]([F:11])[CH:6]=1)[OH:4].[F:26][C:27]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[C:30]([C:37](O)=[O:38])=[CH:29][CH:28]=1.Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1>C(#N)C.O>[F:26][C:27]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[C:30]([C:37]([NH:1][CH:2]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([O:19][C:20]([F:24])([F:25])[CH:21]([F:22])[F:23])[CH:14]=2)[CH:3]([C:5]2[CH:10]=[CH:9][N:8]=[C:7]([F:11])[CH:6]=2)[OH:4])=[O:38])=[CH:29][CH:28]=1

참가 물질

7

반응물 4

HCID 684484-Fluoro-1-naphthoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 22261630(1RS,2SR)-2-amino-1-(2-fluoropyridin-4-yl)-3-(3-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-propanol

생성물 1

HCID 222616024-fluoro-N-{(1RS,2SR)-2-(2-fluoropyridin-4-yl)-2-hydroxy-1-[3-(1,1,2,2-tetrafluoroethoxy)benzyl]ethyl}-1-naphthamide

시약·촉매·용매 2

HCID 962Water용매HCID 6342Acetonitrile용매

실험 절차

To a solution of (1RS,2SR)-2-amino-1-(2-fluoropyridin-4-yl)-3-[3-(1,1,2,2-tetrafluoroethoxy)phenyl]propan-1-ol (194 mg, 0.54 mmol) in acetonitrile (20 ml) were added 4-fluoronaphthalenecarboxylic acid (101 mg, 0.54 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (154 mg, 0.80 mmol) and 1-hydroxybenzotriazole hydrate (82 mg, 0.54 mmol), and the mixture was stirred overnight at room temperature. The reaction solution was diluted with water (100 ml) and extracted with ethyl acetate (100 ml×2). The extract was washed successively with water and saturated brine, dried (anhydrous magnesium sulfate) and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1-ethyl acetate). Recrystallization from ethyl acetate-hexane gave the objective substance (189 mg, 66%).

후처리

  1. extractionextracted with ethyl acetate (100 ml×2)
  2. washThe extract was washed successively with water and saturated brine
  3. dry with materialdried (anhydrous magnesium sulfate)
  4. customevaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1-ethyl acetate)
  6. customRecrystallization from ethyl acetate-hexane
  7. customgave the objective substance (189 mg, 66%)

출처 및 근거

ORD 기록
ord-1b0fe9720cf649d980515bf350b69d24
출처 데이터셋
uspto-grants-2006_01
특허 번호
US06982348B2

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