Ethyl chloroformate → 4-methyl-5,6-dihydro-4H-1,3a,6-triaza-as-indacene-8-carboxylic acid (2-fluoro-4-isopropoxyphenyl)amide

HRID 497390

Reaktionsgleichung

Reaktionsgleichung von HRID 497390
ClC(OCC)=O.Br.[CH3:8][CH:9]1[CH2:20][C:19]2[NH:18][CH:17]=[C:16]([C:21]([OH:23])=O)[C:15]=2[C:14]2[N:10]1[CH:11]=[CH:12][N:13]=2.[F:24][C:25]1[CH:31]=[C:30]([O:32][CH:33]([CH3:35])[CH3:34])[CH:29]=[CH:28][C:26]=1[NH2:27].C(=O)([O-])[O-].[K+].[K+]>C(OCC)(=O)C.O.C(O)C.CN(C)C=O.C(N(CC)CC)C>[F:24][C:25]1[CH:31]=[C:30]([O:32][CH:33]([CH3:34])[CH3:35])[CH:29]=[CH:28][C:26]=1[NH:27][C:21]([C:16]1[C:15]2[C:14]3[N:10]([CH:11]=[CH:12][N:13]=3)[CH:9]([CH3:8])[CH2:20][C:19]=2[NH:18][CH:17]=1)=[O:23]

Komponenten

10

Edukt 4

HCID 10928Ethyl chloroformateHCID 11430Potassium CarbonateHCID 37563842-Fluoro-4-isopropoxyanilineHCID 697358864-methyl-5,6-dihydro-4H-1,3a,6-triaza-as-indacene-8-carboxylic acid hydrobromide

Produkt 1

HCID 865883154-methyl-5,6-dihydro-4H-1,3a,6-triaza-as-indacene-8-carboxylic acid (2-fluoro-4-isopropoxyphenyl)amide

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 702EthanolLösungsmittelHCID 962WaterLösungsmittel2×HCID 6228DimethylformamideLösungsmittelHCID 8471TriethylamineLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

Ethyl chloroformate (66 μL) is added dropwise to an ice-cold mixture of 4-methyl-5,6-dihydro-4H-1,3a,6-triaza-as-indacene-8-carboxylic acid hydrobromide (192 mg), triethylamine (0.33 mL), and N,N-dimethylformamide (5 mL). The mixture is stirred at 0° for 1 hour then at room temperature for 30 minutes. 2-Fluoro-4-isopropoxyaniline (66 mg) is added and the mixture is stirred at room temperature for 18 hours. The mixture is diluted with ethyl acetate (50 mL) then treated with water (25 mL), and extracted with ethyl acetate (3×50 mL). The combined organic layers are washed with water (2×20 mL) and brine (1×20 mL), dried over magnesium sulfate, and concentrated in vacuo. The residue is purified by preparative thin layer chromatography on silica gel, eluting with diethyl ether, to give a brown solid. This is treated with ethanol (2 mL) and saturated aqueous potassium carbonate solution (1 mL) and the mixture is heated at 60° for 30 minutes. The mixture is cooled to room temperature and diluted with water (3 mL) and extracted with ethyl acetate (3×30 mL). The combined organic layers are washed with brine (1×10 mL), dried over magnesium sulfate, and concentrated in vacuo. The oily residue is purified by preparative thin layer chromatography on silica gel, eluting with 10% methanol in dichloromethane, to give 4-methyl-5,6-dihydro-4H-1,3a,6-triaza-as-indacene-8-carboxylic acid (2-fluoro-4-isopropoxyphenyl)amide, pale yellow solid, 10 mg: LRMS calcd 368.40, found [M+H] 369.2.

Aufarbeitung

  1. waitat room temperature for 30 minutes
  2. stirringthe mixture is stirred at room temperature for 18 hours
  3. extractionextracted with ethyl acetate (3×50 mL)
  4. washThe combined organic layers are washed with water (2×20 mL) and brine (1×20 mL)
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue is purified by preparative thin layer chromatography on silica gel
  8. washeluting with diethyl ether
  9. customto give a brown solid
  10. temperaturethe mixture is heated at 60° for 30 minutes
  11. extractionextracted with ethyl acetate (3×30 mL)
  12. washThe combined organic layers are washed with brine (1×10 mL)
  13. dry with materialdried over magnesium sulfate
  14. concentrationconcentrated in vacuo
  15. customThe oily residue is purified by preparative thin layer chromatography on silica gel
  16. washeluting with 10% methanol in dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-3475cdbe015b45e184781002446c3deb
Quelldatensatz
uspto-grants-2005_09
Patentnummer
US06949562B2

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