Sodium Carbonate → HCID 86723591, compound

HRID 918919Notes

Reaction equation

HRID 918919 reaction equation
[CH2:1]([N:8]1[CH:17]=[C:16](I)[C:15]2[C:10](=[CH:11][CH:12]=[N: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.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[C:10](=[CH:11][CH:12]=[N: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 10340Sodium CarbonateHCID 27343463,5-Dimethylisoxazole-4-boronic acidHCID 86723590HCID 86723590, compound

Product 1

HCID 86723591HCID 86723591, compoundYield 32%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
95 °C

Procedure

A mixture of 2-benzyl-4-iodo-2,6-naphthyridin-1(2H)-one (0.070 g, 0.19 mmol), (3,5-dimethylisoxazol-4-yl)boronic acid (0.041 g, 0.29 mmol) and Na2CO3 (0.062 g, 0.58 mmol) in toluene (15 mL), ethanol (15 mL) and water (2 mL) was degassed. Pd(PPh3)4 (0.022 g, 0.19 μmol) was then added and the reaction was heated at 95° C. for 17 h. After that time the reaction was cooled to rt, concentrated under reduced pressure and diluted with ethyl acetate (30 mL). The organic phase was washed with water then brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The product was purified by flash column chromatography (silica gel, 99:1 dichloromethane/methanol) followed by trituration with diethyl ether to give 2-benzyl-4-(3,5-dimethylisoxazol-4-yl)-2,6-naphthyridin-1(2H)-one (0.020 g, 32%) as an off-white solid: mp 159-161° C.; 1H NMR (400 MHz, CDCl3) δ 8.78 (d, J=5.4 Hz, 1H), 8.65 (s, 1H), 8.30 (d, J=5.4 Hz, 1H), 7.30-7.40 (m, 5H), 7.04 (s, 1H), 5.26 (s, 2H), 2.26 (s, 3H), 2.09 (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 (30 mL)
  5. washThe organic phase was washed with water
  6. dry with materialbrine, dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe product was purified by flash column chromatography (silica gel, 99:1 dichloromethane/methanol)

Sources & evidence

ORD record
ord-8fb9ad000e6c422b856f2de4fc5d2b61
Source dataset
uspto-grants-2016_03
Patent number
US09271978B2

Reaction notes

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