Sodium Carbonate → HCID 86723585, compound

HRID 918913Notes

Reaction equation

HRID 918913 reaction equation
[CH2:1]([N:8]1[CH:17]=[C:16](Br)[C:15]2[N:14]=[CH:13][CH:12]=[CH:11][C:10]=2[C:9]1=[O:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:20][C:21]1[C:25](B(O)O)=[C:24]([CH3:29])[O:23][N:22]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([N:8]1[CH:17]=[C:16]([C:25]2[C:21]([CH3:20])=[N:22][O:23][C:24]=2[CH3:29])[C:15]2[N:14]=[CH:13][CH:12]=[CH:11][C:10]=2[C:9]1=[O:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27343463,5-Dimethylisoxazole-4-boronic acidHCID 86723584HCID 86723584, compound

Product 1

HCID 86723585HCID 86723585, compoundYield 66.2%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of 6-benzyl-8-bromo-1,6-naphthyridin-5(6H)-one (0.260 g, 0.82 mmol), (3,5-dimethylisoxazol-4-yl)boronic acid (0.174 g, 1.24 mmol) and Na2CO3 (0.262 g, 2.47 mmol) in toluene (25 mL), ethanol (15 mL) and water (5 mL) was degassed. Pd(PPh3)4 (0.095 g, 0.08 mmol) was then added and the reaction heated at 95° C. for 17 h. After that time the reaction was cooled to rt and concentrated under reduced pressure. The residue was dissolved in ethyl acetate (100 mL), washed with water and brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The product was purified by flash column chromatography (silica gel, 99:1 ethyl acetate/methanol) to give 6-benzyl-8-(3,5-dimethylisoxazol-4-yl)-1,6-naphthyridin-5(6H)-one (0.180 g, 66%) as a white solid: mp 192-195° C.; 1H NMR (400 MHz, CDCl3) δ 8.92 (dd, J=4.5, 1.9 Hz, 1H), 8.78 (dd, J=8.0, 1.9 Hz, 1H), 7.47 (dd, J=8.0, 4.5 Hz, 1H), 7.30-7.41 (m, 5H), 7.20 (s, 1H), 5.27 (s, 2H), 2.25 (s, 3H), 2.11 (s, 3H); ESI MS m/z 332 [M+H]+.

Workup

  1. customwas degassed
  2. temperatureAfter that time the reaction was cooled to rt
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe residue was dissolved in ethyl acetate (100 mL)
  5. washwashed with water and brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe product was purified by flash column chromatography (silica gel, 99:1 ethyl acetate/methanol)

Sources & evidence

ORD record
ord-b4558f5217f047fbb73c5e60bec38d38
Source dataset
uspto-grants-2016_03
Patent number
US09271978B2

Reaction notes

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