Sodium Bicarbonate → HCID 178425145, compound

HRID 1522416Notes

Reaction equation

HRID 1522416 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[N:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH2:6][CH2:5]2.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:3]=[C:4]3[C:9](=[N:8][C:7](=[O:12])[CH2:6][CH2:5]3)[NH:10][CH:11]=2)[CH:38]=1)=[O:50]

Participants

10

Reactant 5

HCID 516892Sodium BicarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 110963256-Bromo-3,4-dihydro-1,8-naphthyridin-2(1H)-oneHCID 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 178425145HCID 178425145, compound

Reagents, catalysts & solvents 4

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

Conditions

Temperature
100 °C

Procedure

6-Bromo-3,4-dihydro-1,8-naphthyridin-2(1H)-one (200 mg, 0.881 mmol) (J. Med. Chem. 2003; 46; 9; 1627-1635), bis(pinacolato)diboron (268 mg, 1.057 mmol), Pd(dppf) (35.7 mg, 0.044 mmol) and potassium acetate (259 mg, 2.64 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 (329 mg, 0.881 mmol), bis(triphenylphosphine)palladium(II) chloride (71.9 mg, 0.088 mmol) and sodium bicarbonate (222 mg, 2.64 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: 5% MeOH/CH2Cl2) to furnish the desired product as a grey solid after evaporation and preciptation from warm EtOAc/MeOH (1:9). The product was collected as 55 mg (13%). LCMS E-S (M+H)=486.3 1H NMR (400 MHz, DMSO-d6) δ ppm 11.57 (br. s., 1 H), 10.74 (s, 1 H), 8.99 (d, J=2.27 Hz, 1 H), 8.93 (t, J=4.93 Hz, 1 H), 8.44 (d, J=1.77 Hz, 1 H), 8.37 (s, 1 H), 8.16 (s, 1 H), 5.91 (s, 1 H), 5.29-5.40 (m, 1 H), 4.42 (d, J=5.05 Hz, 2 H), 3.04 (t, J=7.58 Hz, 2 H), 2.53-2.62 (m, 2 H), 2.23 (s, 3 H), 2.13 (s, 3 H), 1.54 (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: 5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-65c0cee63e75445fbdcaabfc22e5205d
Source dataset
uspto-grants-2015_07
Patent number
US09073924B2

Reaction notes

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