Methyl Isocyanate → 10,11-dihydro-5-methyl-11-methylcarbamyl-5H-pyrido[3,4-f]pyrrolo[1,2-b][1,2,5]triazepine

HRID 982326Notes

Reaction equation

HRID 982326 reaction equation
[CH3:1][N:2]1[C:8]2[CH:9]=[CH:10][N:11]=[CH:12][C:7]=2[NH:6][CH2:5][C:4]2=[CH:13][CH:14]=[CH:15][N:3]12.[CH3:16][N:17]=[C:18]=[O:19]>C1C=CC=CC=1>[CH3:1][N:2]1[C:8]2[CH:9]=[CH:10][N:11]=[CH:12][C:7]=2[N:6]([C:18](=[O:19])[NH:17][CH3:16])[CH2:5][C:4]2=[CH:13][CH:14]=[CH:15][N:3]12

Participants

4

Reactant 2

HCID 12228Methyl IsocyanateHCID 1460194810,11-dihydro-5-methyl-5H-pyrido[3,4-f]pyrrolo[1,2-b][1,2,5]triazepine

Product 1

HCID 1460195610,11-dihydro-5-methyl-11-methylcarbamyl-5H-pyrido[3,4-f]pyrrolo[1,2-b][1,2,5]triazepine

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Conditions

Temperature
70 °C

Procedure

A solution of 3.7 g of 10,11-dihydro-5-methyl-5H-pyrido[3,4-f]pyrrolo[1,2-b][1,2,5]triazepine in 100 ml of benzene was treated with 1.6 ml of methyl isocyanate and then stirred at 70° C. for five hours. After cooling, the mixture was evaporated under reduced pressure and the residue was dissolved in water. The aqueous layer extracted with ethyl acetate. The combined organic layer was washed with water followed by a saturated sodium chloride solution, dried over anhydrous magnesium sulfate, filtered and concentrated. Purification of the residue was achieved by means of high pressure liquid chromatography (silica gel; elution with 2.5% methanol/dichloromethane) to afford 2.3 g of 10,11-dihydro-5-methyl-11-methylcarbamyl-5H-pyrido[3,4-f]pyrrolo[1,2-b][1,2,5]triazepine m.p. 197°-200° C. (dec.). The solid was dissolved in ethanol and acidified with an ethanol solution of maleic acid to precipitate the corresponding maleate salt. Recrystallization of the salt from ethanol yielded 1.8 g of 10,11-dihydro-5-methyl-11 -methylcarbamyl-5H-pyrido[3,4-f]pyrrolo[1,2-b][1,2,5]triazepine maleate, m.p. 160°-161° C.

Workup

  1. temperatureAfter cooling
  2. customthe mixture was evaporated under reduced pressure
  3. dissolutionthe residue was dissolved in water
  4. extractionThe aqueous layer extracted with ethyl acetate
  5. washThe combined organic layer was washed with water
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification of the residue
  10. washwas achieved by means of high pressure liquid chromatography (silica gel; elution with 2.5% methanol/dichloromethane)

Sources & evidence

ORD record
ord-8d7cbc06f6074220a7514988c4bd0fc1
Source dataset
uspto-grants-1991_02
Patent number
US04996205

Reaction notes

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