Dimethylformamide → HCID 58019992, compound

HRID 1632089Notes

Reaction equation

HRID 1632089 reaction equation
[CH3:1][C:2]1[C:6](B(O)O)=[C:5]([CH3:10])[O:4][N:3]=1.[CH:11](=[CH:18][C:19]([CH:21]=[CH:22][C:23]1C=CC=CC=1)=[O:20])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[C:29]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:48](=[O:51])([O-])[O-].[Na+].[Na+].CN(C)[CH:56]=[O:57]>[Pd]>[O:57]1[C:21]2[CH:22]=[CH:23][C:11]([C:12]3[CH:13]=[C:14]([CH:15]=[CH:16][C:17]=3[O:51][CH3:48])[CH2:29][C:6]3[C:2]([CH3:1])=[N:3][O:4][C:5]=3[CH3:10])=[CH:18][C:19]=2[O:20][CH2:56]1

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 95417Dibenzylidene acetoneHCID 27343463,5-Dimethylisoxazole-4-boronic acid

Product 1

HCID 58019992HCID 58019992, compound

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Procedure

To a solution of I-168 (138 mg, 0.500 mmol) and 3,5-dimethyl-isoxazole-4-boronic acid (70 mg, 0.500 mmol) in dimethyl formamide (5 mL) were added palladium(0) bis(dibenzylideneacetone (14 mg, 0.025 mmol), triphenylphosphine (13 mg, 0.0500 mmol) and 1 M aqueous sodium carbonate (1.5 mL, 1.5 mmol). The resultant suspension was stirred at 85° C. for 72 h. The reaction was concentrated under reduced pressure, diluted with ethyl acetate (10 mL), washed with water (3×10 mL) and brine, dried over sodium sulfate, filtered, and the solvent removed under reduced pressure. The crude residue was purified by silica gel preparatory thin layer chromatography eluting with 1:1 hexanes and dichloromethane to afford 16.2 mg (10%) of P-062. 1H NMR (400 MHz, CDCl3) 2.11 (s, 3H), 2.31 (s, 3H), 3.64 (s, 2H), 3.79 (s, 3H), 5.98 (s, 2H), 6.80-6.94 (m, 3H), 6.94-7.05 (m, 3H) ppm. LCMS=100% purity. APCI (+)=338.10 (M+1).

Workup

  1. concentrationThe reaction was concentrated under reduced pressure
  2. additiondiluted with ethyl acetate (10 mL)
  3. washwashed with water (3×10 mL) and brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customthe solvent removed under reduced pressure
  7. customThe crude residue was purified by silica gel preparatory thin layer chromatography
  8. washeluting with 1:1 hexanes and dichloromethane
  9. customto afford 16.2 mg (10%) of P-062

Sources & evidence

ORD record
ord-6ec5934df6c24a8e9f1c44fa12553d39
Source dataset
uspto-grants-2014_07
Patent number
US08791267B2

Reaction notes

Loading…