Picolinohydrazide → HCID 13649490, compound

HRID 1982386Notes

Reaction equation

HRID 1982386 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]([NH:9][NH2:10])=O.Cl[C:12]1[C:18]2=[CH:19][CH:20]=[CH:21][N:17]2[CH2:16][C:15]2[CH:22]=[CH:23][CH:24]=[CH:25][C:14]=2[N:13]=1>CN(C)C=O>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[N:13]2[C:14]3[CH:25]=[CH:24][CH:23]=[CH:22][C:15]=3[CH2:16][N:17]3[CH:21]=[CH:20][CH:19]=[C:18]3[C:12]2=[N:10][N:9]=1

Participants

4

Reactant 2

HCID 255881Picolinohydrazide2×HCID 13649489HCID 13649489, compound

Product 1

HCID 13649490HCID 13649490, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

Into a suitable reactor are charged N,N-dimethylformamide (159 kg) and 2-pyridinecarboxylic acid hydrazide (25.2 kg) and the mixture is stirred 10-15 minuted at 20°-25° to give a solution. In a separate suitable reactor are charged N,N-dimethylformamide (97 kg) and 11-chloro-5H-pyrrolo-[2,1-c][1,4]benzodiazepine (34.4 kg). The mixture is stirred for 15-30 minutes at 20°-25° to give a solution. This solution is added over 2-3 hours to the preheated solution of 2-pyridinecarboxylic acid hydrazide in N,N-dimethylformamide at 48° to 52°. Once the addition is complete the reaction mixture is further stirred for 2-3 hours at 48° to 52°. The reaction mixture is then heated for 12-15 hours at 72°-75°. The mixture is then cooled to 15°-20° with stirring. The solid is filtered off and washed with N,N-dimethylformamide (28 L). The solid is then stirred in a 1:1 mixture of water and ethanol (140 L) for 30-60 minutes at 20°-25°. The pH is adjusted to about 7 using concentrated ammonium hydroxide solution. The reaction mixture is stirred for 30-60 minutes at 20°-25°. The solid is filtered off, washed with a mixture of ethanol and water (1:1, 50 L) and vacuum dried (60°-70°) to give the title compound as the free base, m.p. 255°-257°.

Workup

  1. customminuted at 20°-25°
  2. customto give a solution
  3. stirringThe mixture is stirred for 15-30 minutes at 20°-25°
  4. customto give a solution
  5. additionOnce the addition
  6. stirringis further stirred for 2-3 hours at 48° to 52°
  7. temperatureThe reaction mixture is then heated for 12-15 hours at 72°-75°
  8. temperatureThe mixture is then cooled to 15°-20°
  9. stirringwith stirring
  10. filtrationThe solid is filtered off
  11. washwashed with N,N-dimethylformamide (28 L)
  12. stirringThe solid is then stirred in a 1:1 mixture of water and ethanol (140 L) for 30-60 minutes at 20°-25°
  13. stirringThe reaction mixture is stirred for 30-60 minutes at 20°-25°
  14. filtrationThe solid is filtered off
  15. washwashed with a mixture of ethanol and water (1:1, 50 L) and vacuum
  16. customdried (60°-70°)

Sources & evidence

ORD record
ord-90356fab80f346cda38ef9ddb3fe6a10
Source dataset
uspto-grants-1986_06
Patent number
US04596799

Reaction notes

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