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

HRID 481071

反応式

HRID 481071 の反応式
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]

参加物

10

反応物 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

生成物 1

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

試薬・触媒・溶媒 5

HCID 702Ethanol溶媒HCID 962Water溶媒2 回HCID 6228Dimethylformamide溶媒HCID 8471Triethylamine溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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 600 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.

後処理

  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 600 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

出典と根拠

ORDレコード
ord-3b10b75061f6423cbb2b57a73c5421b6
出典データセット
uspto-grants-2003_11
特許番号
US06653471B2

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