Sodium Carbonate → tert-Butyl 4-(6-(tert-butoxycarbonylamino)-5-(5-phenyl-1,3,4-oxadiazol-2-yl)pyridin-3-yl)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 509530Notes

Reaction equation

HRID 509530 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:23]2[O:24][C:25]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[N:26][N:27]=2)[C:5]([N:8]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])C(=O)OC(C)(C)C)=[N:6][CH:7]=1.CC1(C)C(C)(C)OB([C:42]2[CH2:43][CH2:44][N:45]([C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])[CH2:46][CH:47]=2)O1.C(P(CC)CC)C.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.C(Cl)Cl.O.Cl[Pd]Cl>[C:19]([O:18][C:16]([NH:8][C:5]1[N:6]=[CH:7][C:2]([C:42]2[CH2:47][CH2:46][N:45]([C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])[CH2:44][CH:43]=2)=[CH:3][C:4]=1[C:23]1[O:24][C:25]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[N:26][N:27]=1)=[O:17])([CH3:22])([CH3:21])[CH3:20]

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 27365TriethylphosphineHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 67481749tert-Butyl N-[5-bromo-3-(5-phenyl-1,3,4-oxadiazol-2-yl)-2-pyridyl]-N-tert-butoxycarbonyl-carbamate

Product 1

HCID 68104454tert-Butyl 4-(6-(tert-butoxycarbonylamino)-5-(5-phenyl-1,3,4-oxadiazol-2-yl)pyridin-3-yl)-5,6-dihydropyridine-1(2H)-carboxylateYield 47%

Reagents, catalysts & solvents 4

HCID 24290Palladium ChlorideCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of tert-butyl N-[5-bromo-3-(5-phenyl-1,3,4-oxadiazol-2-yl)-2-pyridyl]-N-tert-butoxycarbonyl-carbamate (300 mg, 0.5799 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylate (215.2 mg, 0.6959 mmol), dichloropalladium; triethylphosphane (12.00 mg, 0.02900 mmol) and Na2CO3 (184.4 mg, 1.740 mmol) in DMF (3.000 mL) was heated to 60° C. for 16 hours. Analysis indicated that there was starting material remaining so the reaction was heated to 140° C. in the microwave for a further 2 hours. The reaction mixture was allowed to cool to ambient temperature, diluted with DCM and water and the two layers separated. The organics were washed with 1M NaOH solution, dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was purified by column chromatography (EtOAc/Petroleum ether) to give the desired product that was used directly in the next step without further purification (142 mg, 47% Yield). MS (ES+) 302.31.

Workup

  1. temperatureto cool to ambient temperature
  2. customthe two layers separated
  3. washThe organics were washed with 1M NaOH solution
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe resultant residue was purified by column chromatography (EtOAc/Petroleum ether)

Sources & evidence

ORD record
ord-bacf1db075254aa58a4530659ff18f2b
Source dataset
uspto-grants-2015_08
Patent number
US09096584B2

Reaction notes

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