trans-N,N'-dimethyl-1,2-cyclohexanediamine → methyl 6-methyl-3-(2H-1,2,3-triazol-2-yl)-2-pyridinecarboxylate

HRID 1094774Notes

Reaction equation

HRID 1094774 reaction equation
I[C:2]1[C:3]([C:9]([O:11][CH3:12])=[O:10])=[N:4][C:5]([CH3:8])=[CH:6][CH:7]=1.[NH:13]1[CH:17]=[CH:16][N:15]=[N:14]1.CN[C@@H]1CCCC[C@H]1NC.C([O-])([O-])=O.[Cs+].[Cs+].C(=O)([O-])[O-]>[Cu]I.CN(C=O)C>[CH3:8][C:5]1[N:4]=[C:3]([C:9]([O:11][CH3:12])=[O:10])[C:2]([N:14]2[N:15]=[CH:16][CH:17]=[N:13]2)=[CH:7][CH:6]=1

Participants

7

Reactant 4

HCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 59363641Methyl 3-iodo-6-methylpicolinateHCID 86643148Cs2CO3 carbonateHCID 178418936HCID 178418936, compound

Product 1

HCID 59363722methyl 6-methyl-3-(2H-1,2,3-triazol-2-yl)-2-pyridinecarboxylate

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Procedure

DMF (1.5 ml) was added to a mixture of methyl 3-iodo-6-methyl-2-pyridinecarboxylate D36 (100 mg), 1H-1,2,3-triazole (49.9 mg, 0.722 mmol), (1R,2R)—N,N′-dimethyl-1,2-cyclohexanediamine (10.27 mg, 0.072 mmol), CuI (3.44 mg, 0.018 mmol) and Cs2CO3 carbonate (235 mg, 0.722 mmol) in a microwave vial. The mixture was degassed via three vacuum/nitrogen cycles then irradiated in a single mode microwave reactor to 120° C. for 20 minutes. The mixture was irradiated in a single mode microwave reactor to 120° C. for a further 40 minutes. The reaction mixture was cooled and filtered washing the solids with EtOAc. The solids were dissolved in pH=3 buffer solution (5 ml); UPLC check of this aqueous solution showed it contained a considerable quantity of 6-methyl-3-(2H-1,2,3-triazol-2-yl)-2-pyridinecarboxylic acid. The aqueous phase was extracted repeatedly with DCM; the combined DCM extracts were diluted with MeOH (50 ml) and treated with TMS-diazomethane. The volatiles were evaporated to give a yellow residue that was purified by flash chromatography on silica gel (Biotage, SNAP 10 g column, 10%-50% EtOAc/Cy) to give the title compound D39 (38 mg) as a white solid. UPLC (Basic QC_POS—50-800): rt=0.57 minutes, peak observed: 219 (M+1). C10H10N4O2 requires 218. 1H NMR (400 MHz, CDCl3) δ ppm 8.20 (d, 1 H), 7.87 (s, 2 H), 7.44 (d, 1 H), 3.94 (s, 3 H), 2.71 (s, 3 H).

Workup

  1. customThe mixture was degassed via three vacuum/nitrogen cycles
  2. customthen irradiated in a single mode microwave reactor to 120° C. for 20 minutes
  3. customThe mixture was irradiated in a single mode microwave reactor to 120° C. for a further 40 minutes
  4. temperatureThe reaction mixture was cooled
  5. filtrationfiltered
  6. washwashing the solids with EtOAc
  7. dissolutionThe solids were dissolved in pH=3 buffer solution (5 ml)
  8. extractionThe aqueous phase was extracted repeatedly with DCM
  9. additionthe combined DCM extracts were diluted with MeOH (50 ml)
  10. additiontreated with TMS-diazomethane
  11. customThe volatiles were evaporated
  12. customto give a yellow residue that
  13. customwas purified by flash chromatography on silica gel (Biotage, SNAP 10 g column, 10%-50% EtOAc/Cy)

Sources & evidence

ORD record
ord-01ebded7cf394124a407a52b449db25f
Source dataset
uspto-grants-2012_03
Patent number
US08133908B2

Reaction notes

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