1,1'-Carbonyldiimidazole → HCID 22914578, compound

HRID 1378013Notes

Reaction equation

HRID 1378013 reaction equation
C(N(C(C)C)C(C)C)C.[ClH:10].[N:11]1([CH2:17][C:18]([OH:20])=O)[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1.C(N1C=CN=C1)(N1C=CN=C1)=O.[F:33][C:34]1[CH:35]=[CH:36][C:37]2[N:43]3[CH:44]=[N:45][C:46]([C:47](=[N:49]O)[NH2:48])=[C:42]3[CH2:41][N:40]([CH3:51])[C:39](=[O:52])[C:38]=2[CH:53]=1>CN(C=O)C>[ClH:10].[F:33][C:34]1[CH:35]=[CH:36][C:37]2[N:43]3[CH:44]=[N:45][C:46]([C:47]4[N:48]=[C:18]([CH2:17][N:11]5[CH2:12][CH2:13][O:14][CH2:15][CH2:16]5)[O:20][N:49]=4)=[C:42]3[CH2:41][N:40]([CH3:51])[C:39](=[O:52])[C:38]=2[CH:53]=1

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 177509462-(Morpholin-4-yl)acetic acid hydrochlorideHCID 540046888-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxamidoxime

Product 1

HCID 22914578HCID 22914578, compoundYield 57.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

0.38 ml (2.2 mmol) of N-ethyldiisopropylamine was added to a suspension of 0.4 g (2.2 mmol) of morpholin-4-yl-acetic acid hydrochloride in 4 ml of DMF. 390 mg (2.4 mmol) of 1,1'- carbonyldiimidazole were added portionwise at room temperature, whereupon the solution was stirred at 50° for 30 min. and then treated at room temperature with 0.58 g (2.0 mmol) of 8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxamidoxime. The reaction mixture was heated to 90° for 20 hrs. The solvent was removed in a vacuum, the residue was taken up in 15 ml of water and the solution was extracted several times with ethyl acetate. The combined extracts were dried over sodium sulfate, filtered and evaporated. The crude material was purified by chromatography on silica gel (methylene chloride/methanol 19:1). The solvent was removed in a vacuum, the residue was dissolved in 5 ml of acetonitrile and the solution was made acid by the addition of ethereal HCl solution. The white crystals were filtered off under suction and recrystallized from acetonitrile. There was obtained 0.5 g (54%) of 8-fluoro-5-methyl-3-(5-morpholin-4-ylmethyl-1,2,4-oxadiazol-3-yl)-5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepin-6-one hydrochloride (3:5) of m.p. 198°-205° (dec.).

Workup

  1. temperatureThe reaction mixture was heated to 90° for 20 hrs
  2. customThe solvent was removed in a vacuum
  3. extractionthe solution was extracted several times with ethyl acetate
  4. dry with materialThe combined extracts were dried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude material was purified by chromatography on silica gel (methylene chloride/methanol 19:1)
  8. customThe solvent was removed in a vacuum
  9. dissolutionthe residue was dissolved in 5 ml of acetonitrile
  10. additionby the addition of ethereal HCl solution
  11. filtrationThe white crystals were filtered off under suction
  12. customrecrystallized from acetonitrile

Sources & evidence

ORD record
ord-0d72ff58032e46b695f3f6c1c70b7857
Source dataset
uspto-grants-1997_09
Patent number
US05665718

Reaction notes

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