Pyridine → HCID 67171508, compound

HRID 1506432Notes

Reaction equation

HRID 1506432 reaction equation
[CH3:1][C:2]1([CH3:36])[O:6][CH:5]([C:7]2[CH:8]=[CH:9][C:10]3[C:16]4=[N:17][O:18][C:19]([C:21]5[O:25][N:24]=[C:23]([C:26]6[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=6)[C:22]=5[C:32]([F:35])([F:34])[F:33])(O)[CH:15]4[CH2:14][O:13][C:11]=3[CH:12]=2)[CH2:4][O:3]1.N1C=CC=CC=1.S(Cl)(Cl)=O>C1(C)C=CC=CC=1>[CH3:1][C:2]1([CH3:36])[O:6][CH:5]([C:7]2[CH:8]=[CH:9][C:10]3[C:16]4=[N:17][O:18][C:19]([C:21]5[O:25][N:24]=[C:23]([C:26]6[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=6)[C:22]=5[C:32]([F:35])([F:33])[F:34])=[C:15]4[CH2:14][O:13][C:11]=3[CH:12]=2)[CH2:4][O:3]1

Participants

5

Reactant 3

HCID 1049PyridineHCID 24386Thionyl ChlorideHCID 67172921HCID 67172921, compound

Product 1

HCID 67171508HCID 67171508, compoundYield 124.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a stirred suspension of 7-(2,2-dimethyl-1,3-dioxolan-4-yl)-3-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-3a,4-dihydro-3H-chromeno[4,3-c]isoxazol-3-ol (Preparation 61A, 0.035 g, 0.070 mmol) in anhydrous toluene (1.0 mL) at room temperature was added pyridine (0.012 mL, 0.153 mmol) followed by thionyl chloride (8.64 μl, 0.118 mmol). The reaction mixture was stirred at room temperature for 15 min. and then at 80° C. for 15 min. The reaction mixture was cooled to room temperature and concentrated. The solid residue was diluted with dichloromethane, washed with a saturated aqueous solution of sodium bicarbonate, and dried over anhydrous sodium sulfate. Concentration under reduced pressure afforded a yellow film. The combined crude products were triturated with methanol with sonication. The solid was collected to provide 7-(2,2-dimethyl-1,3-dioxolan-4-yl)-3-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-4H-chromeno[4,3-c]isoxazole (0.042 g, 0.087 mmol, 62% yield) as an off-white solid. The product had an HPLC with a ret. time=3.63 min.−Column: Chromolith SpeedROD 4.6×50 mm (4 min.); Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA. LC/MS M+1=484.9.

Workup

  1. waitat 80° C. for 15 min
  2. temperatureThe reaction mixture was cooled to room temperature
  3. concentrationconcentrated
  4. additionThe solid residue was diluted with dichloromethane
  5. washwashed with a saturated aqueous solution of sodium bicarbonate
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationConcentration under reduced pressure
  8. customafforded a yellow film
  9. customwere triturated with methanol with sonication
  10. customThe solid was collected

Sources & evidence

ORD record
ord-1454a62ec74545c79c55b43f3627863c
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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