Sodium Carbonate → PF-05089771

HRID 46239ノート

反応式

HRID 46239 の反応式
[H-].[Na+].C([N:7]1[C:11]([NH:12]C(=O)C(F)(F)F)=[C:10]([C:19]2[CH:24]=[C:23]([Cl:25])[CH:22]=[CH:21][C:20]=2[OH:26])[CH:9]=[N:8]1)(C)(C)C.[Cl:27][C:28]1[C:29](F)=[CH:30][C:31]([F:50])=[C:32]([S:34]([N:37]([C:45]2[N:46]=[CH:47][S:48][CH:49]=2)C(=O)OC(C)(C)C)(=[O:36])=[O:35])[CH:33]=1.C(=O)([O-])[O-].[K+].[K+].C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O.C(OCC)(=O)C.CO.O>[NH2:12][C:11]1[NH:7][N:8]=[CH:9][C:10]=1[C:19]1[CH:24]=[C:23]([Cl:25])[CH:22]=[CH:21][C:20]=1[O:26][C:29]1[C:28]([Cl:27])=[CH:33][C:32]([S:34]([NH:37][C:45]2[N:46]=[CH:47][S:48][CH:49]=2)(=[O:36])=[O:35])=[C:31]([F:50])[CH:30]=1

参加物

10

反応物 5

HCID 10340Sodium CarbonateHCID 11430Potassium CarbonateHCID 24758Sodium hydrideHCID 59436577HCID 59436577、化合物HCID 59436581Tert-butyl (5-chloro-2,4-difluorophenyl)sulfonyl(thiazol-4-yl)carbamate

生成物 1

HCID 46840946PF-05089771収率 12%

試薬・触媒・溶媒 4

HCID 887Methanol溶媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
55 °C

実験手順

To a suspension of sodium hydride (29 mg, 1.2 mmol) in dimethylformamide (1 mL) was added N-(1-tert-butyl-4-(5-chloro-2-hydroxyphenyl)-1H-pyrazol-5-yl)-2,2,2-trifluoroacetamide (Preparation 209, 239 mg, 0.661 mmol) and stirred for 30 minutes. To this was added tert-butyl 5-chloro-2,4-difluorophenylsulfonyl(thiazol-4-yl)carbamate (Preparation 453, 206 mg, 0.501 mmol) and stirred for 24 hours. After this time only a small amount of product was observed, so potassium carbonate (40 mg, 0.3 mmol) was added and the reaction heated at 55° C. for 3 days. The reaction was cooled, diluted with ethyl acetate and the organic extract washed with water and saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and concentrated in vacuo. Purification by automated flash column chromatography eluting with ethyl acetate:hexanes (gradient 0:1 to 1:0, by volume) afforded fully protected product. This residue was dissolved in methanol (1 mL) and sodium carbonate solution (2 M aqueous, 0.08 mL, 0.2 mmol) and water (0.2 mL) added. The reaction was stirred at room temperature for 6 hours and then heated at 55° C. for 16 hours before concentrating in vacuo and passing through a short silica gel column eluting with methanol:dichloromethane (gradient 0:1 to 1:9, by volume). All product related fractions were combined, concentrated in vacuo, dissolved in methanol (saturated in gaseous hydrogen chloride) and heated at 50° C. for 16 hours. Purification by preparative HPLC afforded the title compound as a white solid, 31 mg, 12% yield.

後処理

  1. stirringstirred for 24 hours
  2. additionwas added
  3. temperatureThe reaction was cooled
  4. extractionthe organic extract
  5. washwashed with water and saturated aqueous sodium chloride solution
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification by automated flash column chromatography
  10. washeluting with ethyl acetate
  11. customhexanes (gradient 0:1 to 1:0, by volume) afforded fully protected product
  12. stirringThe reaction was stirred at room temperature for 6 hours
  13. temperatureheated at 55° C. for 16 hours
  14. concentrationbefore concentrating in vacuo
  15. washeluting with methanol
  16. concentrationconcentrated in vacuo
  17. dissolutiondissolved in methanol (saturated in gaseous hydrogen chloride)
  18. temperatureheated at 50° C. for 16 hours
  19. customPurification by preparative HPLC

出典と根拠

ORDレコード
ord-f33f216c2eaa4744ac6efaf0611d6488
出典データセット
uspto-grants-2013_09
特許番号
US08541588B2

反応ノート

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