Picolinic acid → HCID 57941440, compound

HRID 1437931Notes

Reaction equation

HRID 1437931 reaction equation
[CH3:1][N:2]1[C:10]2[C@@:9]3([CH3:14])[C:11]([CH3:13])([CH3:12])[C@H:6]([CH2:7][CH2:8]3)[C:5]=2[C:4](=[O:15])[NH:3]1.Br[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=1.N1C=CC=CC=1C(O)=O.C(=O)(O)[O-].[K+]>CN(C)C=O.Cl.[Cu]I>[N:18]1[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=1[N:3]1[C:4](=[O:15])[C:5]2[C@@H:6]3[C:11]([CH3:12])([CH3:13])[C@@:9]([CH3:14])([CH2:8][CH2:7]3)[C:10]=2[N:2]1[CH3:1]

Participants

8

Reactant 4

HCID 1018Picolinic acidHCID 79732-BromopyridineHCID 516893Potassium BicarbonateHCID 57941341HCID 57941341, compound2×

Product 1

HCID 57941440HCID 57941440, compoundYield 25.9%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of (4S,7R)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 19; 412 mg, 2 mmol), 2-bromo-pyridine (175 μL, 1.8 mmol), copper(I) iodide (19 mg, 0.1 mmol), picolinic acid (49 mg, 0.4 mmol), and potassium bicarbonate (280 mg, 2.8 mmol) in N,N-dimethylformamide (10 mL) was irradiated in a microwave oven at 220° C. for 30 min. The reaction mixture was diluted with 0.1 M HCl (200 mL) and then extracted with ethyl acetate (200 mL). The organic layer was washed with 0.1 M HCl, 0.25 M NaOH, and brine, then dried (magnesium sulfate), filtered, evaporated and purified using an ISCO system, eluting with 5-60% ethyl acetate/dichloromethane to give (4S,7R)-2-(pyridin-2-yl)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (132 mg, 23%) as a white solid. ES(+)-MS (M+H) 284.

Workup

  1. customwas irradiated in a microwave oven at 220° C. for 30 min
  2. extractionextracted with ethyl acetate (200 mL)
  3. washThe organic layer was washed with 0.1 M HCl, 0.25 M NaOH, and brine
  4. dry with materialdried (magnesium sulfate)
  5. filtrationfiltered
  6. customevaporated
  7. custompurified
  8. washeluting with 5-60% ethyl acetate/dichloromethane

Sources & evidence

ORD record
ord-e275c7950d2f4e419960eaa88cac21ab
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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