Pyridine-4-carbonyl chloride → N-[4-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-phenyl]-isonicotinamide

HRID 643258Notes

Reaction equation

HRID 643258 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:16][C:15]3([CH3:18])[CH2:17][CH:11]2[CH2:12][C:13]([CH3:20])([CH3:19])[CH2:14]3)=[O:9])=[CH:4][CH:3]=1.[C:21](Cl)(=[O:28])[C:22]1[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=1>C1COCC1>[CH3:18][C:15]12[CH2:17][CH:11]([N:10]([C:8]([C:5]3[CH:4]=[CH:3][C:2]([NH:1][C:21](=[O:28])[C:22]4[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=4)=[CH:7][CH:6]=3)=[O:9])[CH2:16]1)[CH2:12][C:13]([CH3:20])([CH3:19])[CH2:14]2

Participants

4

Reactant 2

HCID 417436Pyridine-4-carbonyl chlorideHCID 577868(4-Amino-phenyl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone

Product 1

HCID 11222652N-[4-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-phenyl]-isonicotinamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of (4-amino-phenyl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone (400 mg, 1.47 mmol) in dry THF (25 ml) was added dropwise a solution of isonicotinoyl chloride (312 mg, 2.20 mmol) in dry THF (20 ml). The mixture was stirred for 2 hrs. and evaporated followed by addition of water 20 (ml). The aqueous phase was extracted with EtOAc (2×20 ml) and the combined organic phases were dried (Na2SO4), filtered and evaporated in vacuo. The resulting residue was purified by column chromatography (silica gel) using first EtOAc (300 ml) followed by a 4% mixture of TEA in EtOAc as eluents. Pure fractions were collected and evaporated to dryness. The residue was crystallized from a mixture of diethyl ether (20 ml) and EtOAc (5 ml) affording after filtering and drying in vacuo at 50° C. 200 mg (36%) of the title compound as a solid.

Workup

  1. customand evaporated
  2. additionfollowed by addition of water 20 (ml)
  3. extractionThe aqueous phase was extracted with EtOAc (2×20 ml)
  4. dry with materialthe combined organic phases were dried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe resulting residue was purified by column chromatography (silica gel)
  8. customPure fractions were collected
  9. customevaporated to dryness
  10. customThe residue was crystallized from a mixture of diethyl ether (20 ml) and EtOAc (5 ml)
  11. customaffording
  12. filtrationafter filtering
  13. customdrying in vacuo at 50° C

Sources & evidence

ORD record
ord-83f102a499b541da9e36e023ad5a8cbc
Source dataset
uspto-grants-2010_04
Patent number
US07700583B2

Reaction notes

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