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

HRID 600323

Reaction equation

HRID 600323 reaction equation
[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]

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 2724231Bis(1,2-bis(diphenylphosphino)ethane)palladium(0)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
75 °C

Procedure

(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).

Workup

  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

Sources & evidence

ORD record
ord-83f88fc889f04917b3c7e5a600d23bf5
Source dataset
uspto-grants-2011_03
Patent number
US07902181B2

Linked notes

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