4-Aminotetrahydropyran → HCID 56598278, compound

HRID 1522389Notes

Reaction equation

HRID 1522389 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.[O: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][O:27][CH2:28][CH2:29]2)[CH:3]=1)=[O:15]

Participants

4

Reactant 2

HCID 4192234-AminotetrahydropyranHCID 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 56598278HCID 56598278, compoundYield 65.6%

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 tetrahydro-2H-pyran-4-amine (2 ml, 19 mmol) in EtOH (3 mL). The vessel was sealed and the reaction mixture was irradiated (microwave) at 125° C. for 2 hr. and then at 170° C. for 1 hr. The mixture was concentrated to ca. 20% volume and NMP (2 mL) added to the reaction mixture. The contents were again irradiated (microwave) first at 180° C. for 2.5 h and then at 190° C. for 75 min. The mixture was evaporated under vacuum, and the resulting residue was purified by silica gel chromatography (eluent: gradient 0 to 90:10:1 DCM/MeOH/NH4OH). The isolated product was treated with EtOAc/hexanes (1:1), sonicated, and heated. After cooling, solids that precipitated were filtered and dried to afford the title compound (46 mg, 64%) as an off-white solid. LCMS E-S (M+H)=439.1. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.55 (s, 1 H) 8.44 (t, J=5.05 Hz, 1 H) 7.83 (s, 1 H) 7.20 (d, J=7.33 Hz, 1 H) 6.63 (s, 1 H) 5.89 (s, 1 H) 4.93 (quin, J=6.69 Hz, 1 H) 4.32 (d, J=5.05 Hz, 2 H) 3.99-4.06 (m, 1 H) 3.88 (dt, J=11.49, 3.47 Hz, 2 H) 3.45 (td, J=11.37, 2.02 Hz, 2 H) 2.21 (s, 3 H) 2.13 (s, 3 H) 1.95 (d, J=10.61 Hz, 2 H) 1.41-1.51 (m, 8 H).

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 2 hr
  4. concentrationThe mixture was concentrated to ca. 20% volume and NMP (2 mL)
  5. additionadded to the reaction mixture
  6. customThe contents were again irradiated (microwave) first at 180° C. for 2.5 h
  7. waitat 190° C. for 75 min
  8. customThe mixture was evaporated under vacuum
  9. customthe resulting residue was purified by silica gel chromatography (eluent: gradient 0 to 90:10:1 DCM/MeOH/NH4OH)
  10. additionThe isolated product was treated with EtOAc/hexanes (1:1)
  11. customsonicated
  12. temperatureheated
  13. temperatureAfter cooling
  14. customsolids that precipitated
  15. filtrationwere filtered
  16. customdried

Sources & evidence

ORD record
ord-f7c9455ecb00453ba83c18561d0b4bb1
Source dataset
uspto-grants-2015_07
Patent number
US09073924B2

Reaction notes

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