Benzoyl chloride → HCID 10431153, compound

HRID 1736704Notes

Reaction equation

HRID 1736704 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.C(N(C(C)C)CC)(C)C.CN(C1C=CC=CN=1)C.[C:41](Cl)(=[O:48])[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1>C1COCC1>[C:41]([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:48])[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1

Participants

6

Reactant 4

HCID 7412Benzoyl chloride2×HCID 218852-DimethylaminopyridineHCID 81531DiisopropylethylamineHCID 10108645HCID 10108645, compound

Product 1

HCID 10431153HCID 10431153, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To 3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-6-fluoro-4,5-dihydroimidazo[1,5-a]quinoxaline (XXXIII, EXAMPLE 103, 0.438 g), diisopropylethylamine (0.26 ml), and dimethylamino-pyridine (0.018 g) in THF (20 ml) is added benzoyl chloride (0.19 ml). After stirring for 5 hr, additional benzoyl chloride (0.20 ml) is added. The reaction is stirred at 20°-25° for 2 hr, then stored over the weekend in the freezer. It is then stirred again at 20°-25° for 24 hr, after which the THF solvent is removed under reduced pressure and replaced with dichloromethane. After stirring for a final 7 hr, the reaction is partitioned between dichloromethane and aqueous sodium bicarbonate. The phases are separated and the organic phase is filtered through sodium sulfate, concentrated, and the crude product chromatographed on silica gel (300 ml) eluting with ethyl acetate/dichloromethane (20/80). The appropriate fractions are pooled and concentrated to give the product which is recrystallized from dichloromethane and hexane to give the title compound, nip 234.5°-235.5°; MS m/z at 401; IR (mineral oil) 1660, 1502, 1366, 786 and 1247 cm-1 ; NMR (CDCl3) 1.21, 2.20, 5.32, 6.98, 7.3-7.5 and 8.19 δ.

Workup

  1. stirringThe reaction is stirred at 20°-25° for 2 hr
  2. stirringIt is then stirred again at 20°-25° for 24 hr
  3. customafter which the THF solvent is removed under reduced pressure
  4. stirringAfter stirring for a final 7 hr
  5. customthe reaction is partitioned between dichloromethane and aqueous sodium bicarbonate
  6. customThe phases are separated
  7. filtrationthe organic phase is filtered through sodium sulfate
  8. concentrationconcentrated
  9. customthe crude product chromatographed on silica gel (300 ml)
  10. washeluting with ethyl acetate/dichloromethane (20/80)
  11. concentrationconcentrated
  12. customto give the product which
  13. customis recrystallized from dichloromethane and hexane

Sources & evidence

ORD record
ord-ec46752b1d9d47958023ebcabf248f3d
Source dataset
uspto-grants-1996_07
Patent number
US05541324

Reaction notes

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