Dimethylformamide → (S)-7-bromo-3-(2-fluoro-2-methylpropoxy)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine

HRID 1970323Notes

Reaction equation

HRID 1970323 reaction equation
[NH2:1][C:2]1[O:3][CH2:4][C@:5]2([C:19]3[C:14](=[N:15][CH:16]=[C:17]([OH:20])[CH:18]=3)[O:13][C:12]3[C:7]2=[CH:8][C:9]([Br:21])=[CH:10][CH:11]=3)[N:6]=1.CN(C=O)C.C(=O)([O-])[O-].[Cs+].[Cs+].FC(F)(F)S(O[CH2:39][C:40]([F:43])([CH3:42])[CH3:41])(=O)=O>>[Br:21][C:9]1[CH:8]=[C:7]2[C@@:5]3([CH2:4][O:3][C:2]([NH2:1])=[N:6]3)[C:19]3[C:14](=[N:15][CH:16]=[C:17]([O:20][CH2:39][C:40]([F:43])([CH3:42])[CH3:41])[CH:18]=3)[O:13][C:12]2=[CH:11][CH:10]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 121655342-Fluoro-2-methylpropyl trifluoromethanesulfonateHCID 58466215(S)-2'-amino-7-bromo-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-3-ol

Product 1

HCID 67241788(S)-7-bromo-3-(2-fluoro-2-methylpropoxy)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine

Conditions

Temperature
0 °C

Procedure

A vial was charged with (S)-2′-amino-7-bromo-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-3-ol (750 mg, 2.154 mmol), DMF (8617 μL, 2.154 mmol) and cesium carbonate (2106 mg, 6.46 mmol). The mixture was cooled to 0° C. and 2-fluoro-2-methylpropyl trifluoromethanesulfonate (966 mg, 4.31 mmol) was added. The reaction was removed from the ice bath and stirred at RT for 45 minutes. The reaction was diluted with water (250 mL) and poured into a separatory funnel containing ethyl acetate (250 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (3×100 mL). The combined organic layers were washed with water and then brine, dried over sodium sulfate, filtered and concentrated in vacuo to provide a light yellow 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 (S)-7-bromo-3-(2-fluoro-2-methylpropoxy)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine as a light yellow solid.

Workup

  1. customThe reaction was removed from the ice bath
  2. additionThe reaction was diluted with water (250 mL)
  3. additionpoured into a separatory funnel
  4. additioncontaining ethyl acetate (250 mL)
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with ethyl acetate (3×100 mL)
  7. washThe combined organic layers were washed with water
  8. dry with materialbrine, dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customto provide a light yellow solid
  12. 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-7397a2fa0e174fe88c99b321eb4e8ce4
Source dataset
uspto-grants-2013_04
Patent number
US08426447B2

Reaction notes

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