Ammonium Chloride → 5-Fluoropyridine-2-carboxamide

HRID 228281

반응식

HRID 228281 반응식
[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([OH:10])=O)=[N:6][CH:7]=1.O[N:12]1C(=O)CCC1=O.Cl.CN(C)CCCN=C=NCC.[Cl-].[NH4+]>C1COCC1.CN(C=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([NH2:12])=[O:10])=[N:6][CH:7]=1

참가 물질

7

반응물 4

HCID 25517Ammonium ChlorideHCID 80170N-HydroxysuccinimideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27628765-fluoropyridine-2-carboxylic Acid

생성물 1

HCID 219047545-Fluoropyridine-2-carboxamide수율 80.7%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8028Tetrahydrofuran용매

실험 절차

Take up 5-Fluoropyridine-2-carboxylic acid (3.82 g, 27.1 mmol) in THF (67.7 mL). Add N-hydroxysuccinimide (3.43 g, 29.8 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (5.71 g, 29.8 mmol). Add DMF (15 mL) to dissolve the gum formed. Stir for 3 hours at room temperature before adding ammonium chloride (2.17 g, 40.6 mmol). Bubble in ammonia gas for five minutes. Seal the reaction vessel and stir the reaction mixture overnight before concentrating. Take the solid up in water (150 mL) and extract with ethyl acetate (4×225 mL). Dry the organic layer over Na2SO4 filter and concentrate. Purify by flash chromatography eluting with 25% ethyl acetate, 1% (2.0 M NH3 in methanol) and 74% dichloromethane to give the title compound (3.06 g, 80.7%): TOF MS EI+ 140.0 (M)+, TOF MS EI+ 97.0 (M+H—CONH2)+, HRMS calcd for C6H5N2OF 140.0386, found 140.0394, time 3.41 min; HPLC [YMC-Pack Pro C-18 (150×4.6 nm, S-5 microm), 0.1% TFA/acetonitrile in 0.1% TFA/water at 1.0 mL/min, 5-95% over 19 min], tR=7.1 min, 100% purity.

후처리

  1. customformed
  2. customBubble in ammonia gas for five minutes
  3. customSeal the reaction vessel
  4. stirringstir the reaction mixture overnight
  5. concentrationbefore concentrating
  6. extractionextract with ethyl acetate (4×225 mL)
  7. dry with materialDry the organic layer over Na2SO4
  8. filtrationfilter
  9. concentrationconcentrate
  10. customPurify by flash chromatography
  11. washeluting with 25% ethyl acetate, 1% (2.0 M NH3 in methanol) and 74% dichloromethane

출처 및 근거

ORD 기록
ord-22f38e3ab3e946249ec178457c80b203
출처 데이터셋
uspto-grants-2009_07
특허 번호
US07560463B2

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