Pyrazole → HCID 59363685, compound

HRID 1094772Notes

Reaction equation

HRID 1094772 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][CH:15]=[N:14]1.CN(C)[C@@H]1CCCC[C@H]1N.C(=O)([O-])[O-].[Cs+].[Cs+].[Si](C=[N+]=[N-])(C)(C)C>CN(C=O)C>[CH3:8][C:5]1[N:4]=[C:3]([C:9]([O:11][CH3:12])=[O:10])[C:2]([N:13]2[CH:17]=[CH:16][CH:15]=[N:14]2)=[CH:7][CH:6]=1

Participants

7

Reactant 5

HCID 1048PyrazoleHCID 10796Cesium carbonateHCID 167693TrimethylsilyldiazomethaneHCID 11275066(1R,2R)-N1,N1-Dimethylcyclohexane-1,2-diamineHCID 59363641Methyl 3-iodo-6-methylpicolinate

Product 1

HCID 59363685HCID 59363685, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

DMF (1.5 ml) was added to a mixture of methyl 3-iodo-6-methyl-2-pyridinecarboxylate D36 (200 mg), 1H-pyrazole (98 mg, 1.444 mmol), (1R,2R)—N,N-dimethyl-1,2-cyclohexanediamine (20.54 mg, 0.144 mmol), bis(copper(I) trifluoromethanesulfonate), benzene complex (18.17 mg, 0.036 mmol) and cesium carbonate (470 mg, 1.444 mmol) in a screw-topped vial. The mixture was degassed via 3 vacuum/nitrogen cycles and heated with shaking to 120° C. for 1 hour. The reaction mixture was evaporated to dryness under reduced pressure. The residue was dissolved in water/MeOH (1:1, 3 ml) and acidified to pH=2 by addition of 4 M HCl solution. The resulting mixture was evaporated to dryness under reduced pressure then the residue was triturated with DCM/MeOH (3:1, 20 ml). The mixture was filtered washing with more DCM/MeOH (3:1, 5 ml). The filtrate was treated with TMS-diazomethane solution (2 M in hexanes, 2 ml, 4 mmol) to re-esterify the acid. The reaction mixture was evaporated under reduced pressure and the residue was purified twice by flash chromatography on silica gel (Biotage Snap 10 g column, EtOAc/Cy from 20/80 to 50/50 and then Biotage KP-NH Snap 11 g column, EtOAc/DCM isocratic 1/99) to give the title compound D37 (107 mg) as a colourless gum.

Workup

  1. customThe mixture was degassed via 3 vacuum/nitrogen cycles
  2. temperatureheated
  3. customThe reaction mixture was evaporated to dryness under reduced pressure
  4. dissolutionThe residue was dissolved in water/MeOH (1:1, 3 ml)
  5. additionacidified to pH=2 by addition of 4 M HCl solution
  6. customThe resulting mixture was evaporated to dryness under reduced pressure
  7. customthe residue was triturated with DCM/MeOH (3:1, 20 ml)
  8. filtrationThe mixture was filtered
  9. washwashing with more DCM/MeOH (3:1, 5 ml)
  10. customThe reaction mixture was evaporated under reduced pressure
  11. customthe residue was purified twice by flash chromatography on silica gel (Biotage Snap 10 g column, EtOAc/Cy from 20/80 to 50/50

Sources & evidence

ORD record
ord-bd1a11c5d61a4c829bdce86684342ef1
Source dataset
uspto-grants-2012_03
Patent number
US08133908B2

Reaction notes

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