Potassium Carbonate → (S)-N-((S)-1-Cyano-2-(4'-(N-(2-hydroxyethyl)sulfamoyl)biphenyl-4-yl)ethyl)piperidine-2-carboxamide

HRID 600323

反応式

HRID 600323 の反応式
[C:1]([C@@H:3]([NH:12][C:13]([C@@H:15]1[CH2:20][CH2:19][CH2:18][CH2:17][N:16]1C(OC(C)(C)C)=O)=[O:14])[CH2:4][C:5]1[CH:10]=[CH:9][C:8](I)=[CH:7][CH:6]=1)#[N:2].[Si]([O:35][CH2:36][CH2:37][NH:38][S:39]([C:42]1[CH:47]=[CH:46][C:45](B(O)O)=[CH:44][CH:43]=1)(=[O:41])=[O:40])(C(C)(C)C)(C)C.C(=O)([O-])[O-].[K+].[K+]>C1C=CC(P(C2C=CC=CC=2)CCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)CCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Pd].O1CCOCC1>[C:1]([C@@H:3]([NH:12][C:13]([C@@H:15]1[CH2:20][CH2:19][CH2:18][CH2:17][NH:16]1)=[O:14])[CH2:4][C:5]1[CH:6]=[CH:7][C:8]([C:45]2[CH:44]=[CH:43][C:42]([S:39](=[O:40])(=[O:41])[NH:38][CH2:37][CH2:36][OH:35])=[CH:47][CH:46]=2)=[CH:9][CH:10]=1)#[N:2]

参加物

6

反応物 3

HCID 11430Potassium CarbonateHCID 44119854(4-(N-(2-((tert-Butyldimethylsilyl)oxy)ethyl)sulfamoyl)phenyl)boronic acidHCID 57999629(S)-tert-Butyl 2-((S)-1-cyano-2-(4-iodophenyl)ethylcarbamoyl)piperidine-1-carboxylate

生成物 1

HCID 42640981(S)-N-((S)-1-Cyano-2-(4'-(N-(2-hydroxyethyl)sulfamoyl)biphenyl-4-yl)ethyl)piperidine-2-carboxamide収率 17.6%

試薬・触媒・溶媒 2

HCID 2724231Bis(1,2-bis(diphenylphosphino)ethane)palladium(0)触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
75 °C

実験手順

(S)-tert-Butyl 2-((S)-1-cyano-2-(4-iodophenyl)ethylcarbamoyl)piperidine-1-carboxylate (0.15 g) and bis[1,2-bis(diphenylphosphino)ethane]palladium (0) (2.80 mg, 3.10 μmol) were added to dioxane (3 mL) and 4-(N-(2-(tert-butyldimethylsilyloxy)ethyl)sulfamoyl)-phenylboronic acid (0.167 g) was added to the mixture which was then stirred, under nitrogen, for 10 min. Potassium carbonate (2M solution) (0.310 mL) was added and the reaction mixture was heated at 75° C. for 3 h. The reaction mixture was poured onto a Isolute HM-N cartridge and product was eluted with DCM. Solvent was removed in vacuo and the residue was dissolved in THF (5 mL). The resulting solution was cooled in an ice-bath and TBAF (1M solution in THF, 0.626 mL) was added and stirring was continued for 2 h. The reaction mixture was concentrated in vacuo and dissolved in formic acid (5 mL). The resulting solution was heated at 50° C. for 10 min. The reaction mixture was concentrated in vacuo, dissolved in methanol and loaded onto an SCX cartridge. Non-basic impurities were washed off with methanol then the desired compound was eluted with 10% ammonia in methanol. Solvent was removed in vacuo to give the title compound (0.025 g).

後処理

  1. additionwas added to the mixture which
  2. additionThe reaction mixture was poured onto a Isolute HM-N cartridge and product
  3. washwas eluted with DCM
  4. customSolvent was removed in vacuo
  5. dissolutionthe residue was dissolved in THF (5 mL)
  6. temperatureThe resulting solution was cooled in an ice-bath
  7. additionTBAF (1M solution in THF, 0.626 mL) was added
  8. stirringstirring
  9. waitwas continued for 2 h
  10. concentrationThe reaction mixture was concentrated in vacuo
  11. dissolutiondissolved in formic acid (5 mL)
  12. temperatureThe resulting solution was heated at 50° C. for 10 min
  13. concentrationThe reaction mixture was concentrated in vacuo
  14. dissolutiondissolved in methanol
  15. washNon-basic impurities were washed off with methanol
  16. washthe desired compound was eluted with 10% ammonia in methanol
  17. customSolvent was removed in vacuo

出典と根拠

ORDレコード
ord-83f88fc889f04917b3c7e5a600d23bf5
出典データセット
uspto-grants-2011_03
特許番号
US07902181B2

関連ノート

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