Potassium Carbonate → 6-Amino-4-(cyclohexyloxy)-2-methylnicotinonitrile

HRID 928389Notes

Reaction equation

HRID 928389 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([CH3:8])[C:5]([C:9]#[N:10])=[C:4]([O-:11])[CH:3]=1.[Na+].C([O-])([O-])=O.[K+].[K+].[C:19]1(Br)[CH2:24][CH2:23][CH2:22][CH2:21][CH:20]=1.C([O-])(O)=O.[Na+]>CN(C=O)C.[Pd]>[NH2:1][C:2]1[CH:3]=[C:4]([O:11][CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)[C:5]([C:9]#[N:10])=[C:6]([CH3:8])[N:7]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 5197751-Bromocyclohex-1-eneHCID 58081220Sodium 6-amino-3-cyano-2-methylpyridin-4-olate

Product 1

HCID 667236456-Amino-4-(cyclohexyloxy)-2-methylnicotinonitrile

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 6228DimethylformamideSolvent

Procedure

To a mixture of sodium 6-amino-3-cyano-2-methylpyridin-4-olate (300 mg, 1.75 mmol) and K2CO3 (485 mg, 3.51 mmol) in DMF (6 ml) was added Cyclohexenylbromide (0.213 ml, 1.84 mmol) and the reaction mixture was stirred at it for 14 h. NaHCO3 (100 ml) was added and the mixture was extracted with EA (5×30 ml). The combined organic extracts were dried over Na2SO4, filtered and concentrated. The resulting product was dissolved in n-PrOH (10 ml), and hydrogenated (1 atm H2, rt) for 1 h over Pd/C (93 mg, 0.088 mmol). The reaction mixture was filtered and the filtrate was adsorbed on celite. Purification by column chromatography (CombiFlash Companion, 10 g SiO2, DCM to DCM:MeOH 9:1) afforded the desired product. LCMS RtM=1.63 min, [M+H]+=232.6.

Workup

  1. extractionthe mixture was extracted with EA (5×30 ml)
  2. dry with materialThe combined organic extracts were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. dissolutionThe resulting product was dissolved in n-PrOH (10 ml)
  6. filtrationThe reaction mixture was filtered
  7. customPurification by column chromatography (CombiFlash Companion, 10 g SiO2, DCM to DCM:MeOH 9:1)

Sources & evidence

ORD record
ord-2c8382e268a14b8d9205c5761e0fd2fa
Source dataset
uspto-grants-2016_03
Patent number
US09290485B2

Reaction notes

Loading…