Ammonium Chloride → 5-Fluoropyridine-2-carboxamide

HRID 130830

反応式

HRID 130830 の反応式
[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

参加物

7

反応物 4

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

生成物 1

HCID 219047545-Fluoropyridine-2-carboxamide収率 80.7%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

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+B—CONH2), HRMS calcd for C6H5N2OF 140.0386, found 140.0394, time 3.4 min; HPLC [YMC-Pack Pro C-18 (150×4.6 mm, 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.

後処理

  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

出典と根拠

ORDレコード
ord-c8982c6b86ba4579b4350b27d173d5c6
出典データセット
uspto-grants-2008_06
特許番号
US07381719B2

関連ノート

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