Sodium Sulfate → HCID 86723589, compound

HRID 918917Notes

Reaction equation

HRID 918917 reaction equation
[CH2:1]([N:8]1[CH:17]=[C:16](I)[C:15]2[C:10](=[CH:11][N:12]=[CH:13][CH:14]=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.[O-]S([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[C:10](=[CH:11][N:12]=[CH:13][CH:14]=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 24436Sodium SulfateHCID 27343463,5-Dimethylisoxazole-4-boronic acidHCID 86723588HCID 86723588, compound

Product 1

HCID 86723589HCID 86723589, compoundYield 54%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
95 °C

Procedure

A mixture of 2-benzyl-4-iodo-2,7-naphthyridin-1(2H)-one (0.540 g, 1.49 mmol), (3,5-dimethylisoxazol-4-yl)boronic acid (0.315 g, 2.24 mmol) and Na2SO4 (0.474 g, 4.47 mmol) in toluene (25 mL), ethanol (25 mL) and water (4 mL) was degassed. Pd(PPh3)4 (0.172 g, 0.15 mmol) was then added and the reaction mixture was heated at 95° C. for 6 h. After that time the reaction was cooled to rt, concentrated under reduced pressure and diluted with ethyl acetate (100 mL). The organic phase was washed with water then brine, dried over Na2SO4, and concentrated under reduced pressure. The product was purified by flash column chromatography (silica gel, dichloromethane to 99:1 ethyl acetate/methanol) to give 2-benzyl-4-(3,5-dimethylisoxazol-4-yl)-2,7-naphthyridin-1(2H)-one (0.260 g, 54%) as an off-white solid: mp 174-177° C.; 1H NMR (400 MHz, CDCl3) δ 9.73 (s, 1H), 8.75 (d, J=5.4 Hz, 1H), 7.31-7.41 (m, 5H), 7.16 (s, 1H), 7.02 (d, J=5.4 Hz, 1H), 5.26 (s, 2H), 2.23 (s, 3H), 2.06 (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. additiondiluted with ethyl acetate (100 mL)
  5. washThe organic phase was washed with water
  6. dry with materialbrine, dried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customThe product was purified by flash column chromatography (silica gel, dichloromethane to 99:1 ethyl acetate/methanol)

Sources & evidence

ORD record
ord-a3cb476c68094c7cb2afad016a21bfb4
Source dataset
uspto-grants-2016_03
Patent number
US09271978B2

Reaction notes

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