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

HRID 1970315Notes

Reaction equation

HRID 1970315 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+].[CH2:33](I)[C:34]([CH3:37])([CH3:36])[CH3:35]>O.C(OCC)(=O)C>[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][CH2:33][C:34]([CH3:37])([CH3:36])[CH3:35])[CH:18]=3)[O:13][C:12]2=[CH:11][CH:10]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 84953Propane, 1-iodo-2,2-dimethyl-HCID 58466215(S)-2'-amino-7-bromo-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-3-ol

Product 1

HCID 67240631(S)-7-bromo-3-(neopentyloxy)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
100 °C

Procedure

To a solution of (S)-2′-amino-7-bromo-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-3-ol (390 mg, 1.120 mmol) in DMF (4481 μL, 1.120 mmol) in a sealed tube was added cesium carbonate (912 mg, 2.80 mmol). After stirring for 1 minute neopentyl iodide (223 μL, 1.680 mmol) was added, the reaction vessel was sealed and heated at 100° C. for 2.5 hours. Reaction was cooled to RT to prevent over alkylation. The reaction was diluted with water (25 mL) and 10 mL of ethyl acetate and stirred for 30 minutes before being poured into a separatory funnel containing ethyl acetate (100 mL) and water (250 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (3×50 mL). The aqueous layer was then extracted with DCM (3×50 mL). The organic layers were each washed with water and then brine, at which point all the organics were combined, dried over sodium sulfate, filtered and concentrated in vacuo to provide a brown foam 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-(neopentyloxy)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine as a yellow solid.

Workup

  1. additionwas added
  2. customthe reaction vessel was sealed
  3. customReaction
  4. temperaturewas cooled to RT
  5. additionbefore being poured into a separatory funnel
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted with ethyl acetate (3×50 mL)
  8. extractionThe aqueous layer was then extracted with DCM (3×50 mL)
  9. washeach washed with water
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customto provide a brown foam that
  14. customwas 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-d4f4a12cb6964908bff3e0c232f3821c
Source dataset
uspto-grants-2013_04
Patent number
US08426447B2

Reaction notes

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