N~1~-(Pyridin-2-yl)ethane-1,2-diamine → HCID 56598814, compound

HRID 1522415Notes

Reaction equation

HRID 1522415 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.[NH2:27][CH2:28][CH2:29][NH:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=1>CN1C(=O)CCC1>[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:27][CH2:28][CH2:29][NH:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=2)[CH:3]=1)=[O:15]

Participants

4

Reactant 2

HCID 410428N~1~-(Pyridin-2-yl)ethane-1,2-diamineHCID 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 56598814HCID 56598814, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

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 (80 mg, 0.21 mmol) and (2-aminoethyl)2-pyridinylamine (88 mg, 0.64 mmol) were suspended in 2 mL of NMP and irradiated (microwave) as follows: 180° C. for 30 min, 200° C. for 30 min, 220° C. for 30 min, 230° C. for 30 min and then 240° C. for 1 h. After cooling to room temperature, some of the solvent was removed in vacuo and the residue was purified by silica gel chromatography (eluent: DCM/MeOH/NH4OH, gradient 0 to 90:10:1). The collected solid was partitioned between water and EtOAc/toluene (1:1) and then extracted twice with DCM/isopropanol. The combined organic layers were washed with water, dried over MgSO4, filtered, and concentrated in vacuo to afford a dark brown oil. After drying under vacuum overnight, the residue was again purified by silica gel chromatography (eluent: DCM/MeOH/NH4OH (gradient 0 to 90:10:1). The collected solid was suspended in EtOH, sonicated, and filtered. The solid was further washed with EtOH/DCM, filtered, and dried in vacuum-oven for 2 days. The final product was collected as 47 mg (45%). LCMS E-S (M+H)=475.0 1H NMR (400 MHz, DMSO-d6) δ ppm 11.56 (br. s., 1 H) 8.47 (t, J=5.05 Hz, 1 H) 7.97 (dd, J=4.93, 1.14 Hz, 1 H) 7.85 (s, 1 H) 7.32-7.39 (m, 2 H) 6.65 (s, 1 H) 6.61 (t, J=5.43 Hz, 1 H) 6.46-6.51 (m, 2 H) 5.89 (s, 1 H) 4.97 (quin, J=6.69 Hz, 1 H) 4.32 (d, J=5.05 Hz, 2 H) 3.49 (dt, J=15.28, 5.62 Hz, 4 H) 2.21 (s, 3 H) 2.13 (s, 3 H) 1.44 (s, 3 H) 1.43 (s, 3 H).

Workup

  1. customirradiated (microwave)
  2. wait200° C. for 30 min
  3. wait220° C. for 30 min
  4. wait230° C. for 30 min
  5. wait240° C. for 1 h
  6. customsome of the solvent was removed in vacuo
  7. customthe residue was purified by silica gel chromatography (eluent: DCM/MeOH/NH4OH, gradient 0 to 90:10:1)
  8. customThe collected solid was partitioned between water and EtOAc/toluene (1:1)
  9. extractionextracted twice with DCM/isopropanol
  10. washThe combined organic layers were washed with water
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customto afford a dark brown oil
  15. customAfter drying under vacuum overnight
  16. customthe residue was again purified by silica gel chromatography (eluent
  17. customsonicated
  18. filtrationfiltered
  19. washThe solid was further washed with EtOH/DCM
  20. filtrationfiltered
  21. customdried in vacuum-oven for 2 days
  22. customThe final product was collected as 47 mg (45%)

Sources & evidence

ORD record
ord-cb1f25a776044fe9acc8f0f5c137e804
Source dataset
uspto-grants-2015_07
Patent number
US09073924B2

Reaction notes

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