Acetic Anhydride → HCID 10449849, compound

HRID 1378761Notes

Reaction equation

HRID 1378761 reaction equation
[CH:1]1([C:4]2[O:8][N:7]=[C:6]([C:9]3[N:10]=[CH:11][N:12]4[C:21]5[C:16](=[C:17]([F:22])[CH:18]=[CH:19][CH:20]=5)[NH:15][CH2:14][C:13]=34)[N:5]=2)[CH2:3][CH2:2]1.CN(C1C=CC=CN=1)C.[C:32](OC(=O)C)(=[O:34])[CH3:33]>>[C:32]([N:15]1[C:16]2[C:21](=[CH:20][CH:19]=[CH:18][C:17]=2[F:22])[N:12]2[CH:11]=[N:10][C:9]([C:6]3[N:5]=[C:4]([CH:1]4[CH2:3][CH2:2]4)[O:8][N:7]=3)=[C:13]2[CH2:14]1)(=[O:34])[CH3:33]

Participants

4

Reactant 3

HCID 7918Acetic AnhydrideHCID 218852-DimethylaminopyridineHCID 10108645HCID 10108645, compound

Product 1

HCID 10449849HCID 10449849, compound

Procedure

A solution of 3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-6-fluoro-4,5-dihydroimidazo[1,5-a]quinoxaline (XXXIII, EXAMPLE 103, 0.504 g), dimethylaminopyridine (0.03 g) and acetic anhydride (12 ml) is stirred at 100° for 1 hr. After cooling, excess acetic anhydride is removed under reduced pressure and the residue is partitioned between dichloromethane and aqueous sodium bicarbonate. The phases are separated and the organic phase is dried over sodium sulfate and concentrated. Chromatography on silica gel (320 ml) eluting with methanol/dichloromethane (2/98) gives a poor separation of the product from the imine byproduct. The imine impurity is successfully removed by taking up the mixture in dichloromethane and allowing the imine to precipitate out. The filtrate is collected, concentrated and the product crystallized from dichloromethane and hexane to give the title compound, mp 208.5°-210.0°; MS m/z at 339; IR (mineral oil) 1671, 1503, 1254, 879 and 1204 cm-1 ; NMR (CDCl3) 1.28, 2.38, 2.13, 2.29, 7.16, 7.41 and 8.13 δ.

Workup

  1. temperatureAfter cooling
  2. customexcess acetic anhydride is removed under reduced pressure
  3. customthe residue is partitioned between dichloromethane and aqueous sodium bicarbonate
  4. customThe phases are separated
  5. dry with materialthe organic phase is dried over sodium sulfate
  6. concentrationconcentrated
  7. washChromatography on silica gel (320 ml) eluting with methanol/dichloromethane (2/98)
  8. customgives
  9. customa poor separation of the product from the imine byproduct
  10. customThe imine impurity is successfully removed
  11. customto precipitate out
  12. customThe filtrate is collected
  13. concentrationconcentrated
  14. customthe product crystallized from dichloromethane and hexane

Sources & evidence

ORD record
ord-1f903d1ef7ff4d9f879e0f51c60f7eeb
Source dataset
uspto-grants-1997_09
Patent number
US05668282

Reaction notes

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