Methanol → HCID 67247760, compound

HRID 1970269Notes

Reaction equation

HRID 1970269 reaction equation
[OH:1][C:2]([CH3:26])([CH3:25])[C:3]#[C:4][C:5]1[CH:6]=[C:7]2[C:18]3([CH2:22][O:21][C:20]([NH2:23])=[N:19]3)[C:17]3[C:12](=[N:13][CH:14]=[C:15]([Br:24])[CH:16]=3)[O:11][C:8]2=[CH:9][CH:10]=1.CO.[CH3:29]S(O)(=O)=O.C(OCC)(=O)C>C(=O)(O)[O-].[Na+]>[CH3:29][O:1][C:2]([CH3:26])([CH3:25])[C:3]#[C:4][C:5]1[CH:6]=[C:7]2[C:18]3([CH2:22][O:21][C:20]([NH2:23])=[N:19]3)[C:17]3[C:12](=[N:13][CH:14]=[C:15]([Br:24])[CH:16]=3)[O:11][C:8]2=[CH:9][CH:10]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 6395Methanesulfonic AcidHCID 8857Ethyl AcetateHCID 67247901HCID 67247901, compound

Product 1

HCID 67247760HCID 67247760, compoundYield 87%

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
60 °C

Procedure

To a flask charged with 7-(3-hydroxy-3-methyl-1-butyn-1-yl)-3-bromo-spiro[chromeno[2,3-b]pyridine-5,4′-[1,3]oxazol]-2′-amine (340 mg, 0.821 mmol) was added methanol (9962 μL, 246 mmol) and methane sulfonic acid (533 μL, 8.21 mmol). The flask was sealed and heated at 60° C. for 3 hours. The reaction was diluted with saturated sodium bicarbonate (100 mL) and poured into a separatory funnel containing ethyl acetate (50 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to provide a tan solid that was purified by silica gel chromatography (Redi-Sep pre-packed silica gel column (40 g), 0-10% methanol in methylenechloride with 0.1% ammonium hydroxide) to provide 7-(3-methoxy-3-methyl-1-butyn-1-yl)-3-bromo-spiro[chromeno[2,3-b]pyridine-5,4′-[1,3]oxazol]-2′-amine (306 mg, 0.714 mmol, 87% yield) as a tan solid. MS m/z=428.0 [M+H]+. Calc'd for C20H19BrN3O3: 428.1.

Workup

  1. customThe flask was sealed
  2. additionpoured into a separatory funnel
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with ethyl acetate (3×50 mL)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto provide a tan solid
  10. customthat was purified by silica gel chromatography (Redi-Sep pre-packed silica gel column (40 g), 0-10% methanol in methylenechloride with 0.1% ammonium hydroxide)

Sources & evidence

ORD record
ord-50505e935288442f95e212c34c3f9523
Source dataset
uspto-grants-2013_04
Patent number
US08426447B2

Reaction notes

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