Hydrochloric Acid → HCID 76283196, compound

HRID 923525Notes

Reaction equation

HRID 923525 reaction equation
[F:1][C:2]1[CH:38]=[CH:37][CH:36]=[C:35]([F:39])[C:3]=1[CH2:4][O:5][C:6]1[C:7]2[N:8]([C:12]([C:16]([NH:18][C:19]3([C:27]4[N:28]=[N:29][N:30]([CH:32]([F:34])[F:33])[N:31]=4)[CH2:24][O:23]C(C)(C)[O:21][CH2:20]3)=[O:17])=[C:13]([CH3:15])[N:14]=2)[CH:9]=[CH:10][CH:11]=1.FC1C=CC=C(F)C=1COC1C2N(C(C(NC3(C4N(C(F)F)N=NN=4)COC(C)(C)OC3)=O)=C(C)N=2)C=CC=1.Cl.C(OC(C)C)(C)C>C(OCC)(=O)C.CO>[F:1][C:2]1[CH:38]=[CH:37][CH:36]=[C:35]([F:39])[C:3]=1[CH2:4][O:5][C:6]1[C:7]2[N:8]([C:12]([C:16]([NH:18][C:19]([C:27]3[N:28]=[N:29][N:30]([CH:32]([F:34])[F:33])[N:31]=3)([CH2:20][OH:21])[CH2:24][OH:23])=[O:17])=[C:13]([CH3:15])[N:14]=2)[CH:9]=[CH:10][CH:11]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 7914Diisopropyl EtherHCID 118308720HCID 118308720, compoundHCID 118308750HCID 118308750, compound

Product 1

HCID 76283196HCID 76283196, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

23.6 g of a mixture of 8-[(2,6-difluorobenzyl)oxy]-N-{5-[2-(difluoromethyl)-2H-tetrazol-5-yl]-2,2-dimethyl-1,3-dioxan-5-yl}-2-methylimidazo[1,2-a]pyridine-3-carboxamide and 8-[(2,6-difluorobenzyl)oxy]-N-{5-[1-(difluoromethyl)-1H-tetrazol-5-yl]-2,2-dimethyl-1,3-dioxan-5-yl}-2-methylimidazo[1,2-a]pyridine-3-carboxamide, a mixture of 220 ml of methanol and 220 ml of 1 M hydrochloric acid was stirred at room temperature for 14 hours. The reaction mixture was concentrated under reduced pressure and a saturated aqueous sodium hydrogen carbonate solution was added thereto, followed by extraction with chloroform/methanol=9:1. The organic layer was washed with a saturated aqueous sodium chloride solution and dried over anhydrous sodium sulfate, and the solvent was then evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 15.1 g of a crude product. To this crude product were added 30 ml of ethyl acetate and 150 ml of diisopropyl ether, followed by stirring at room temperature for 1 hour. The insoluble materials were separated by filtration, and the solid was washed with 100 ml of diisopropyl ether and dried under reduced pressure to obtain 12.9 g of 8-[(2,6-difluorobenzyl)oxy]-N-{2-[2-(difluoromethyl)-2H-tetrazol-5-yl]-1,3-dihydroxypropan-2-yl}-2-methylimidazo[1,2-a]pyridine-3-carboxamide.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additiona saturated aqueous sodium hydrogen carbonate solution was added
  3. extractionfollowed by extraction with chloroform/methanol=9:1
  4. washThe organic layer was washed with a saturated aqueous sodium chloride solution
  5. dry with materialdried over anhydrous sodium sulfate
  6. customthe solvent was then evaporated under reduced pressure
  7. customThe obtained residue was purified by silica gel column chromatography
  8. customto obtain 15.1 g of a crude product
  9. stirringby stirring at room temperature for 1 hour
  10. customThe insoluble materials were separated by filtration
  11. washthe solid was washed with 100 ml of diisopropyl ether
  12. customdried under reduced pressure

Sources & evidence

ORD record
ord-1750f2e7be8548ae84aefb6c9d3b7c69
Source dataset
uspto-grants-2016_03
Patent number
US09278968B2

Reaction notes

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