Phosgene → HCID 11793365, compound

HRID 1736701Notes

Reaction equation

HRID 1736701 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.[CH:23]([N:26]([CH:29](C)C)[CH2:27]C)(C)C.C(Cl)(Cl)=[O:33].Cl.CNC.C(=O)(O)[O-].[Na+]>C1COCC1>[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)[N:15]([C:27]([N:26]([CH3:29])[CH3:23])=[O:33])[CH2:14][C:13]=34)[N:5]=2)[CH2:3][CH2:2]1

Participants

7

Reactant 5

HCID 6371PhosgeneHCID 10473Dimethylamine, hydrochlorideHCID 81531Diisopropylethylamine2×HCID 516892Sodium BicarbonateHCID 10108645HCID 10108645, compound

Product 1

HCID 11793365HCID 11793365, 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, 0.520 g) in THF (15 ml) is added diisopropylethylamine (0.305 ml) followed by phosgene (1.2M in toluene, 2.19 ml). After stirring for 3 hr, dimethylamine hydrochloride (0.285 g) is added followed by diisopropylethylamine (0.91 ml). The reaction is stirred for 3 hr, after which several ml of aqueous sodium bicarbonate is added. The reaction is concentrated under reduced pressure and the residue partitioned between dichloromethane, aqueous sodium bicarbonate and saline. The phases are separated, the organic phase is dried over sodium sulfate and concentrated. The solid is chromatographed on silica gel (150 ml) eluting with methanol/dichloromethane (2/98). The appropriate fractions are pooled and concentrated to give a solid, which is recrystallized from dichloromethane and hexane to give the title compound, mp 194°-195°; MS m/z at 368; IR (mineral oil) 1657, 1502, 1391, 786 and 1224 cm-1 ; NMR (CDCl3) 1.25, 1.36, 2.25, 2.94, 5.05, 7.08, 7.21, 7.37, 8.11 δ.

Workup

  1. stirringThe reaction is stirred for 3 hr
  2. concentrationThe reaction is concentrated under reduced pressure
  3. customthe residue partitioned between dichloromethane, aqueous sodium bicarbonate and saline
  4. customThe phases are separated
  5. dry with materialthe organic phase is dried over sodium sulfate
  6. concentrationconcentrated
  7. customThe solid is chromatographed on silica gel (150 ml)
  8. washeluting with methanol/dichloromethane (2/98)
  9. concentrationconcentrated
  10. customto give a solid, which
  11. customis recrystallized from dichloromethane and hexane

Sources & evidence

ORD record
ord-b3acad7a4e8a4d9a8bf2061baeac41ff
Source dataset
uspto-grants-1996_07
Patent number
US05541324

Reaction notes

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