Sodium Bicarbonate → N-[(4,6-Dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-6-{6-[(methylamino)sulfonyl]-3-pyridinyl}-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

HRID 1522417Notes

Reaction equation

HRID 1522417 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([S:8]([NH:11][CH3:12])(=[O:10])=[O:9])=[N:6][CH:7]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].Cl[C:37]1[CH:38]=[C:39]([C:49]([NH:51][CH2:52][C:53]2[C:54](=[O:61])[NH:55][C:56]([CH3:60])=[CH:57][C:58]=2[CH3:59])=[O:50])[C:40]2[CH:45]=[N:44][N:43]([CH:46]([CH3:48])[CH3:47])[C:41]=2[N:42]=1.C(=O)(O)[O-].[Na+]>O1CCOCC1.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.O.COCCOC>[CH3:59][C:58]1[CH:57]=[C:56]([CH3:60])[NH:55][C:54](=[O:61])[C:53]=1[CH2:52][NH:51][C:49]([C:39]1[C:40]2[CH:45]=[N:44][N:43]([CH:46]([CH3:48])[CH3:47])[C:41]=2[N:42]=[C:37]([C:2]2[CH:7]=[N:6][C:5]([S:8]([NH:11][CH3:12])(=[O:10])=[O:9])=[CH:4][CH:3]=2)[CH:38]=1)=[O:50]

Participants

10

Reactant 5

HCID 516892Sodium BicarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 565974256-Chloro-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamideHCID 584364765-Bromo-N-methyl-2-pyridinesulfonamide

Product 1

HCID 56598940N-[(4,6-Dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-6-{6-[(methylamino)sulfonyl]-3-pyridinyl}-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

5-Bromo-N-methyl-2-pyridinesulfonamide (225 mg, 0.896 mmol), Bis(pinacolato)diboron (296 mg, 1.165 mmol), Pd(dppf) (35.7 mg, 0.044 mmol) and potassium acetate (264 mg, 2.69 mmol) were suspended in 1,4-Dioxane (8 mL), and stirred with heating at 100° C. for 1 h. After cooling to room temperature, 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 (368 mg, 0.986 mmol), bis(triphenylphosphine)palladium(II) chloride (73.2 mg, 0.090 mmol) and sodium bicarbonate (226 mg, 2.69 mmol) were added, followed by DME (5 mL) and water (3 mL). The reaction mixture was irradiated (microwave) at 120° C. for 2 h. The reaction mixture was cooled to room temperature and filtered through Na2SO4. The contents were purified directly by silica gel chromatography (eluent: 15% MeOH/CH2Cl2) to furnish the desired product as a grey solid after evaporation and preciptation from warm EtOAc/MeOH (1:9). The product was again purified by silica gel chromatography (eluent: 5% MeOH/CH2Cl2) to afford the final product as a white solid, 83 mg (18%). LCMS E-S (M+H)=510.0 1H NMR (400 MHz, DMSO-d6) δ ppm 11.59 (br. s., 1 H), 9.56 (d, J=1.52 Hz, 1 H), 8.96 (s, 1 H), 8.86 (dd, J=8.34, 2.27 Hz, 1 H), 8.46 (s, 1 H), 8.34 (s, 1 H), 8.12 (d, J=8.34 Hz, 1 H), 7.85 (br. s., 1 H), 5.91 (s, 1 H), 5.27-5.46 (m, 1 H), 4.43 (d, J=4.80 Hz, 2 H), 2.60 (s, 3 H), 2.23 (s, 3 H), 2.13 (s, 3 H), 1.56 (d, 6 H).

Workup

  1. temperatureAfter cooling to room temperature
  2. customThe reaction mixture was irradiated (microwave) at 120° C. for 2 h
  3. temperatureThe reaction mixture was cooled to room temperature
  4. filtrationfiltered through Na2SO4
  5. customThe contents were purified directly by silica gel chromatography (eluent: 15% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-b532ed0dc3f547eb91c333d8f54c1760
Source dataset
uspto-grants-2015_07
Patent number
US09073924B2

Reaction notes

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