Sodium Carbonate → HCID 86723583, compound

HRID 918909Notes

Reaction equation

HRID 918909 reaction equation
[CH2:1]([N:8]1[N:17]=[C:16](Cl)[C:15]2[C:10](=[CH:11][CH: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](B2OC(C)(C)C(C)(C)O2)=[C:24]([CH3:35])[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[N:17]=[C:16]([C:25]2[C:21]([CH3:20])=[N:22][O:23][C:24]=2[CH3:35])[C:15]2[C:10](=[CH:11][CH: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 10340Sodium CarbonateHCID 27586563,5-Dimethylisoxazole-4-boronic acid pinacol esterHCID 24751992HCID 24751992, compound

Product 1

HCID 86723583HCID 86723583, compoundYield 23.5%

Reagents, catalysts & solvents 4

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

Procedure

A mixture of 2-benzyl-4-chloro-2H-phthalazin-1-one (1.35 g, 5 mmol), 3,5-dimethyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)isoxazole (1.34 g, 6 mmol), Pd(PPh3)4 (0.58 g, 0.5 mmol) and Na2CO3 (1.59 g, 15 mmol) in toluene (25 mL), ethanol (12.5 mL) and water (12.5 mL) was degassed and heated to reflux with stirring for 18 h. After that time, the mixture was cooled to rt and diluted with ethyl acetate (80 mL). The organic phase was separated, washed with water and brine, dried over MgSO4 and concentrated under reduced pressure. The resulting semi-solid was triturated with hexanes to give a yellow solid. The product was purified by flash column chromatography (silica gel, 80:20 hexanes/ethyl acetate) followed by recrystallization from CHCl3/hexanes to give 2-benzyl-4-(3,5-dimethylisoxazol-4-yl)phthalazin-1(2H)-one (0.39 g, 23%) as a white solid: mp 186-188° C.; 1H NMR (400 MHz, CDCl3) δ 8.55-8.53 (m, 1H), 7.83-7.76 (m, 2H), 7.48 (d, J=7.2 Hz, 2H), 7.44-7.42 (m, 1H), 7.35-7.26 (m, 3H), 5.45 (s, 2H), 2.31 (s, 3H), 2.15 (s, 3H).

Workup

  1. customwas degassed
  2. temperatureheated
  3. temperatureto reflux
  4. additiondiluted with ethyl acetate (80 mL)
  5. customThe organic phase was separated
  6. washwashed with water and brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting semi-solid was triturated with hexanes
  10. customto give a yellow solid
  11. customThe product was purified by flash column chromatography (silica gel, 80:20 hexanes/ethyl acetate)
  12. customfollowed by recrystallization from CHCl3/hexanes

Sources & evidence

ORD record
ord-1c7508a320f74f5e94fed7ca14669428
Source dataset
uspto-grants-2016_03
Patent number
US09271978B2

Reaction notes

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