Phosgene → 3-(5-Cyclopropyl-1,2,4-oxadiazol-3-yl)-4,5-dihydro-5-[(morpholino)carbonyl]imidazo[1,5-a]quinoxaline

HRID 1736695Notes

Reaction equation

HRID 1736695 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](=[CH:17][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.[C:31](Cl)(Cl)=[O:32].[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1>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](=[CH:17][CH:18]=[CH:19][CH:20]=5)[N:15]([C:31]([N:35]5[CH2:40][CH2:39][O:38][CH2:37][CH2:36]5)=[O:32])[CH2:14][C:13]=34)[N:5]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 6371PhosgeneHCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 99937443-(5-Cyclopropyl-1,2,4-oxadiazol-3-yl)-4,5-dihydroimidazo[1,5-a]quinoxaline

Product 1

HCID 106205233-(5-Cyclopropyl-1,2,4-oxadiazol-3-yl)-4,5-dihydro-5-[(morpholino)carbonyl]imidazo[1,5-a]quinoxaline

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a slurry consisting of 3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)4,5-dihydroimidazo[1,5-a]quinoxaline (XXXIII, EXAMPLE 88, 0.499 g), diisopropylethylamine (0.81 ml) and THF (15 ml) is added phosgene (1.93 M in toluene, 1.20 ml). A slight exotherm ensues and the slurry becomes homogeneous. After 10 min, morpholine (0.20 ml) is added. The mixture is stirred for 2 hr and then partitioned between ethyl acetate, water, and saline. The phases are separated and the organic phase is dried over magnesium sulfate and concentrated. The crude product is chromatographed on silica gel (150 ml) eluting with methanol/dichloromethane (2/98). The appropriate fractions are pooled and concentrated to give the product. Recrystallization from dichloromethane and hexane gives the title compound, mp 198.0°-198.5°; MS (m/z) at 392; IR 1662, 1506, 1409, 1277, and 1579 cm-1 ; NMR (CDCl3) 1.24, 1.36, 2.27, 3.33, 3.64, 5.02, 7.21, 7.27, 7.55 and 8.11 δ.

Workup

  1. custompartitioned between ethyl acetate, water, and saline
  2. customThe phases are separated
  3. dry with materialthe organic phase is dried over magnesium sulfate
  4. concentrationconcentrated
  5. customThe crude product is chromatographed on silica gel (150 ml)
  6. washeluting with methanol/dichloromethane (2/98)
  7. concentrationconcentrated
  8. customto give the product
  9. customRecrystallization from dichloromethane and hexane

Sources & evidence

ORD record
ord-775ef40e23c6472c9ce17248c436e2f0
Source dataset
uspto-grants-1996_07
Patent number
US05541324

Reaction notes

Loading…