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

HRID 1899937Notes

Reaction equation

HRID 1899937 reaction equation
F[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=O)[C:6]([CH3:14])(C)[NH:5]2.[CH3:15][C:16]([CH3:19])([O-])C.[K+].P(Cl)(OCC)(OCC)=O.[N:30]#[C-:31].[O:32]1[CH:36]=CN=[N:33]1.C[N:38]([CH:40]=O)C>C1COCC1>[CH:19]1([C:36]2[O:32][N:33]=[C:31]([C:14]3[N:38]=[CH:40][N:5]4[C:4]5[C:9](=[CH:10][CH:11]=[CH:2][CH:3]=5)[NH:8][CH2:7][C:6]=34)[N:30]=2)[CH2:16][CH2:15]1

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 13139Diethyl chlorophosphateHCID 229128926-Fluoro-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-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 (1.0 M 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 tiltrate 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-32b22b80bd00468eaf05f1d3ca8b4ed2
Source dataset
uspto-grants-1996_11
Patent number
US05574038

Reaction notes

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