Sodium Carbonate → N-[(4,6-Dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-1-(1-methylethyl)-6-[6-(4-methyl-1-piperazinyl)-3-pyridinyl]-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

HRID 475974Notes

Reaction equation

HRID 475974 reaction equation
Cl[C:2]1[CH:3]=[C:4]([C:15]([NH:17][CH2:18][C:19]2[C:20](=[O:27])[NH:21][C:22]([CH3:26])=[CH:23][C:24]=2[CH3:25])=[O:16])[C:5]2[C:10]([CH3:11])=[N:9][N:8]([CH:12]([CH3:14])[CH3:13])[C:6]=2[N:7]=1.[CH3:28][N:29]1[CH2:34][CH2:33][N:32]([C:35]2[CH:40]=[CH:39][C:38](B3OC(C)(C)C(C)(C)O3)=[CH:37][N:36]=2)[CH2:31][CH2:30]1.C(=O)([O-])[O-].[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CS(C)=O>[CH3:25][C:24]1[CH:23]=[C:22]([CH3:26])[NH:21][C:20](=[O:27])[C:19]=1[CH2:18][NH:17][C:15]([C:4]1[C:5]2[C:10]([CH3:11])=[N:9][N:8]([CH:12]([CH3:14])[CH3:13])[C:6]=2[N:7]=[C:2]([C:38]2[CH:37]=[N:36][C:35]([N:32]3[CH2:31][CH2:30][N:29]([CH3:28])[CH2:34][CH2:33]3)=[CH:40][CH:39]=2)[CH:3]=1)=[O:16]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27696181-Methyl-4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)piperazineHCID 565974266-Chloro-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

Product 1

HCID 56597428N-[(4,6-Dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-1-(1-methylethyl)-6-[6-(4-methyl-1-piperazinyl)-3-pyridinyl]-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

To a 10-mL microwave vial were added 6-chloro-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide (70 mg, 0.180 mmol),1-methyl-4-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridinyl]piperazine (71.1 mg, 0.235 mmol), DMSO (2.0 mL) and sodium carbonate (0.271 mL, 0.541 mmol) and the mixture was degassed for 10 min under nitrogen. Bis(triphenylphosphine)palladium(II) chloride (10.13 mg, 0.014 mmol) was added and the contents were sealed. The mixture was irradiated (microwave) at 140° C. for 8 h. The reaction mixture was then quenched with water (5 mL) and filtered. The crude product was washed with water, dried, and then purified via silica gel chromatography (eluent: gradient of 0 to 15% (9:1 MeOH/NH4OH)/DCM). The resulting product was treated with MeOH and 1N HCl. The mixture was concentrated in vacuo, dried under high vacuum and collected as the HCl salt, 42 mg (36%). LCMS E-S (M+H)=529.0 1H NMR (400 MHz, DMSO-d6) δ ppm 1.50 (d, 6H), 2.13 (s, 3H), 2.25 (s, 3H), 2.42 (s, 3H), 2.81 (d, J=4.55 Hz, 3H), 3.03-3.21 (m, 2H), 3.41 (br. s., 2H), 3.52 (d, J=11.37 Hz, 2H), 4.39 (d, J=5.05 Hz, 2H), 4.56 (d, J=14.40 Hz, 2H), 5.23 (quin, J=6.63 Hz, 1H), 5.91 (s, 1H), 7.19 (d, J=9.09 Hz, 1H), 7.68 (s, 1H), 8.50 (dd, J=9.09, 2.27 Hz, 1H), 8.73 (t, J=4.93 Hz, 3H), 8.98 (d, J=2.02 Hz, 3H), 10.97-11.21 (m, 2H)

Workup

  1. customthe mixture was degassed for 10 min under nitrogen
  2. customthe contents were sealed
  3. customThe mixture was irradiated (microwave) at 140° C. for 8 h
  4. customThe reaction mixture was then quenched with water (5 mL)
  5. filtrationfiltered
  6. washThe crude product was washed with water
  7. customdried
  8. custompurified via silica gel chromatography (eluent: gradient of 0 to 15% (9:1 MeOH/NH4OH)/DCM)
  9. additionThe resulting product was treated with MeOH and 1N HCl
  10. concentrationThe mixture was concentrated in vacuo
  11. customdried under high vacuum
  12. customcollected as the HCl salt, 42 mg (36%)

Sources & evidence

ORD record
ord-1c3faba957c14ac59a0f1077d9bfaed0
Source dataset
uspto-grants-2014_01
Patent number
US08637509B2

Reaction notes

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