Dimethylformamide → 3-(5-Cyclopropyl-1,2,4-oxadiazol-3-yl)-4,5-dihydroimidazo[1,5-a]quinoxaline

HRID 1378752Notes

Reaction equation

HRID 1378752 reaction equation
[C:1]([N:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[NH:12][C:11](=O)[CH2:10]1)(=O)C1C=CC=CC=1.[CH3:20][C:21]([CH3:24])([O-])C.[K+].P(Cl)(OCC)(OCC)=O.[N:35]#[C-].O1[CH:41]=[CH:40][N:39]=N1.C[N:43]([CH:45]=[O:46])C>C1COCC1>[CH:24]1([C:45]2[O:46][N:35]=[C:41]([C:40]3[N:39]=[CH:1][N:9]4[C:18]5[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=5)[NH:12][CH2:11][C:10]=34)[N:43]=2)[CH2:21][CH2:20]1

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 13139Diethyl chlorophosphateHCID 7343784-Benzoyl-1,2,3,4-tetrahydroquinoxalin-2-oneHCID 23665647Potassium tert-butoxide2×HCID 86749983Oxadiazole isocyanide

Product 1

HCID 99937443-(5-Cyclopropyl-1,2,4-oxadiazol-3-yl)-4,5-dihydroimidazo[1,5-a]quinoxaline

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of the 1,2,3,4-tetrahydroquinoxalin-2-one (IV, 5.51 g) and THF (55 ml) is cooled to -40°, and potassium tert-butoxide (1.0M in THF, 34.8 ml) is added dropwise over 5 min. The mixture is allowed to warm to -20° over 1 hr. DMF (10 ml) and THF (40 ml) are added to the resultant solid, allowing the mixture to stir. The mixture is cooled to -50°, and diethyl chlorophosphate (5.02 ml) is added dropwise over 5 min. The mixture is allowed to warm to -20° over 1 hr. The mixture is cooled to -78°, and the oxadiazole isocyanide (5.70 g) is added. Potassium tert-butoxide (34.8 ml) is added dropwise over 15 min, the mixture is allowed to warm slowly to 20°-25°, and is stirred for 3 days at 20°-25°. The mixture is quenched with water, filtered, washed with water and dried to provide the desired material as a solid. Additional solids that precipitated from the filtrate are filtered, triturated with ethyl acetate/hexane (20/80) and dried to give the title compound, mp 243°-245°; NMR (CDCl3) 8.07, 7.42, 7.10, 6.8-6.9, 4.81, 4.08, 2.2-2.3 and 1.2-1.4 δ.

Workup

  1. temperatureto warm to -20° over 1 hr
  2. temperatureThe mixture is cooled to -50°
  3. temperatureto warm to -20° over 1 hr
  4. temperatureThe mixture is cooled to -78°
  5. temperatureto warm slowly to 20°-25°
  6. stirringis stirred for 3 days at 20°-25°
  7. customThe mixture is quenched with water
  8. filtrationfiltered
  9. washwashed with water
  10. customdried

Sources & evidence

ORD record
ord-4c40702c1a6b435797f207e7eb540a59
Source dataset
uspto-grants-1997_09
Patent number
US05668282

Reaction notes

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