Benzophenone imine → 2-amino-N-benzyl-6-methoxyisonicotinamide

HRID 714279Notes

Reaction equation

HRID 714279 reaction equation
[CH2:1]([NH:8][C:9](=[O:19])[C:10]1[CH:15]=[C:14]([O:16][CH3:17])[N:13]=[C:12](Cl)[CH:11]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=[NH:33])(C1C=CC=CC=1)C1C=CC=CC=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[NH2:33][C:12]1[CH:11]=[C:10]([CH:15]=[C:14]([O:16][CH3:17])[N:13]=1)[C:9]([NH:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:19]

Participants

7

Reactant 3

HCID 136809Benzophenone imineHCID 23676156Sodium t-butoxideHCID 58247770N-benzyl-2-chloro-6-methoxyisonicotinamide

Product 1

HCID 582478622-amino-N-benzyl-6-methoxyisonicotinamideYield 62.2%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

To a degassed mixture of N-benzyl-2-chloro-6-methoxyisonicotinamide (1.38 g, 5.00 mmol), benzophenone imine (1.0 mL, 5.78 mmol), sodium t-butoxide (1.20 g, 12.0 mmol) and rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.02 g, 0.03 mmol) in toluene (40 mL) was added tris(dibenzylideneacetone)dipalladium (0.01 g, 0.01 mmol). The resulting solution was heated at 90° C. for 18 hours and concentrated in vacuo. The residue was dissolved in a mixture of tetrahydrofuran (20 mL) and 10% hydrochloric acid solution (20 mL) and stirred for 20 hours at ambient temperature. The resulting solution was neutralized with saturated sodium bicarbonate solution until pH 8-9 and extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine (30 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography to give 2-amino-N-benzyl-6-methoxyisonicotinamide (0.80 g, 62%): MS (ES+) m/z 258.5 (M+1).

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in a mixture of tetrahydrofuran (20 mL) and 10% hydrochloric acid solution (20 mL)
  3. extractionextracted with ethyl acetate (3×50 mL)
  4. washThe combined organic layers were washed with brine (30 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-224c61da0a2f4eb099cd132b280b4af4
Source dataset
uspto-grants-2015_11
Patent number
US09187426B2

Reaction notes

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