4-Pyridinemethanamine → HCID 56597294, compound

HRID 475998Notes

Reaction equation

HRID 475998 reaction equation
Cl[C:2]1[CH:3]=[C:4]([C:14]([NH:16][CH2:17][C:18]2[C:19](=[O:26])[NH:20][C:21]([CH3:25])=[CH:22][C:23]=2[CH3:24])=[O:15])[C:5]2[CH:10]=[N:9][N:8]([CH:11]([CH3:13])[CH3:12])[C:6]=2[N:7]=1.[N:27]1[CH:32]=[CH:31][C:30]([CH2:33][NH2:34])=[CH:29][CH:28]=1>CCO>[CH3:24][C:23]1[CH:22]=[C:21]([CH3:25])[NH:20][C:19](=[O:26])[C:18]=1[CH2:17][NH:16][C:14]([C:4]1[C:5]2[CH:10]=[N:9][N:8]([CH:11]([CH3:13])[CH3:12])[C:6]=2[N:7]=[C:2]([NH:34][CH2:33][C:30]2[CH:31]=[CH:32][N:27]=[CH:28][CH:29]=2)[CH:3]=1)=[O:15]

Participants

4

Reactant 2

HCID 773174-Pyridinemethanamine2×HCID 565974256-Chloro-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

Product 1

HCID 56597294HCID 56597294, compoundYield 36.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

In a 25 mL sealable tube under nitrogen were combined 6-chloro-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide (60 mg, 0.16 mmol) and (4-pyridinylmethyl)amine (0.065 ml, 0.64 mmol) in EtOH (2 mL). The vessel was sealed and the reaction mixture was heated at 90° C. overnight. An additional 1 mL of (4-pyridinylmethyl) amine was added and the mixture was heated in a microwave at 160° C. for 90 min. The EtOH solvent was removed under reduced pressure, 2 mL of NMP was added, and the mixture was then irradiated (microwave) at 180° C. for 90 min. The mixture was evaporated under vacuum, and the resulting residue was partitioned between EtOAc and water. The crude residue was extracted with EtOAc, DCM and DCM/isopropanol (70:30). The combined organics were washed with water (2×) and brine, dried over MgSO4, filtered and evaporated. The residue was purified by silica gel chromatography (eluent: gradient 0 to 90:10:1 DCM/MeOH/NH4OH). The isolated yellow oil was treated with EtOAc and sonicated. The filtered solid was washed with hexanes and dried to afford the title compound (26 mg, 36%) as a white solid. LCMS E-S (M+H)=446.1. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.56 (s, 1H) 8.50 (t, J=5.18 Hz, 1H) 8.43-8.48 (m, 2H) 7.89 (t, J=5.94 Hz, 1H) 7.84 (s, 1H) 7.34 (d, J=6.06 Hz, 2H) 6.73 (s, 1H) 5.89 (s, 1H) 4.83 (quin, J=6.69 Hz, 1H) 4.58 (d, J=5.81 Hz, 2H) 4.32 (d, J=5.05 Hz, 2H) 2.21 (s, 3H) 2.13 (s, 3H) 1.32 (d, J=6.82 Hz, 6H).

Workup

  1. customIn a 25 mL sealable tube under nitrogen were combined
  2. customThe vessel was sealed
  3. temperaturethe mixture was heated in a microwave at 160° C. for 90 min
  4. customThe EtOH solvent was removed under reduced pressure, 2 mL of NMP
  5. additionwas added
  6. customthe mixture was then irradiated (microwave) at 180° C. for 90 min
  7. customThe mixture was evaporated under vacuum
  8. customthe resulting residue was partitioned between EtOAc and water
  9. extractionThe crude residue was extracted with EtOAc, DCM and DCM/isopropanol (70:30)
  10. washThe combined organics were washed with water (2×) and brine
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. customevaporated
  14. customThe residue was purified by silica gel chromatography (eluent: gradient 0 to 90:10:1 DCM/MeOH/NH4OH)
  15. additionThe isolated yellow oil was treated with EtOAc
  16. customsonicated
  17. washThe filtered solid was washed with hexanes
  18. customdried

Sources & evidence

ORD record
ord-cecfeaa796194da68d923475810b81f7
Source dataset
uspto-grants-2014_01
Patent number
US08637509B2

Reaction notes

Loading…