4-Piperidinamine → HCID 56598147, compound

HRID 475996Notes

Reaction equation

HRID 475996 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.[NH:27]1[CH2:32][CH2:31][CH:30]([NH2:33])[CH2:29][CH2:28]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:33][CH:30]2[CH2:31][CH2:32][NH:27][CH2:28][CH2:29]2)[CH:3]=1)=[O:15]

Participants

4

Reactant 2

HCID 4243614-PiperidinamineHCID 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 56598147HCID 56598147, compoundYield 35%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

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-piperidinamine (2 mL) in EtOH (3 mL). The vessel was sealed and the reaction mixture was irradiated (microwave) at 125° C. for 5 hr and then at 160° C. for 90 min. The mixture was evaporated under vacuum and the resulting residue was partitioned between EtOAc and water. 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 product was treated with EtOAc/ether (1:1) and allowed to stand at room temperature overnight. The solids that had precipitated were triturated, filtered, and dried to afford the title compound as a pale yellow solid 25 mg (35%). LCMS E-S (M+H)=438.0. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.66 (t, J=4.67 Hz, 1H) 7.98 (s, 1H) 7.12 (s, 1H) 5.89 (s, 1H) 4.98 (dt, J=13.33, 6.60 Hz, 1H) 4.30-4.41 (m, 4H) 3.01 (t, J=11.62 Hz, 2H) 2.85 (br. s., 1H) 2.20 (s, 3H) 2.12 (s, 3H) 1.80 (d, J=10.36 Hz, 2H) 1.44 (s, 3H) 1.43 (s, 3H) 1.18-1.30 (m, 3H) 0.79-0.91 (m, 1H)

Workup

  1. customIn a 25 mL sealable tube under nitrogen were combined
  2. customThe vessel was sealed
  3. customthe reaction mixture was irradiated (microwave) at 125° C. for 5 hr
  4. customThe mixture was evaporated under vacuum
  5. customthe resulting residue was partitioned between EtOAc and water
  6. washOrganics were washed with water (2×) and brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue was purified by silica gel chromatography (eluent: gradient 0 to 90:10:1 DCM/MeOH/NH4OH)
  11. additionThe isolated product was treated with EtOAc/ether (1:1)
  12. waitto stand at room temperature overnight
  13. customThe solids that had precipitated
  14. customwere triturated
  15. filtrationfiltered
  16. customdried

Sources & evidence

ORD record
ord-1d8bbf4e0cde43a6bc65837d7d970977
Source dataset
uspto-grants-2014_01
Patent number
US08637509B2

Reaction notes

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