Dimethylformamide → Pirodavir

HRID 484510Notes

Reaction equation

HRID 484510 reaction equation
Cl[C:2]1[N:3]=[N:4][C:5]([CH3:8])=[CH:6][CH:7]=1.C(O)(=O)CCC(O)=O.[NH:17]1[CH2:22][CH2:21][CH:20]([CH2:23][CH2:24][O:25][C:26]2[CH:36]=[CH:35][C:29]([C:30]([O:32][CH2:33][CH3:34])=[O:31])=[CH:28][CH:27]=2)[CH2:19][CH2:18]1.C(=O)([O-])[O-].[Na+].[Na+].CN(C)C=O>ClCCl.O>[CH3:8][C:5]1[N:4]=[N:3][C:2]([N:17]2[CH2:18][CH2:19][CH:20]([CH2:23][CH2:24][O:25][C:26]3[CH:27]=[CH:28][C:29]([C:30]([O:32][CH2:33][CH3:34])=[O:31])=[CH:35][CH:36]=3)[CH2:21][CH2:22]2)=[CH:7][CH:6]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 2272543-Chloro-6-methylpyridazineHCID 23056112Ethyl 4-[2-(4-piperidinyl)ethoxy]benzoate butanedioate

Product 1

HCID 71345PirodavirYield 56.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 10.4 parts of 3-chloro-6-methylpyridazine, 22.4 parts of ethyl 4-[2-(4-piperidinyl)ethoxy]benzoate butanedioate (1:1), 8.6 parts of sodium carbonate and 0.9 parts of N,N-dimethylformamide was stirred for 3 hours in an oil bath at ±150° C. After cooling, water and dichloromethane were added and the layers were separated. The organic layer was dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and ethanol (99:1 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from a mixture of 2,2'-oxybixpropane and 2-propanone (75:25 by volume). The precipitated product as filtered off and dried, yielding 17 parts (56.8%) of ethyl 4-[2-[1-(6-methyl-3-pyridazinyl)-4-piperidinyl]ethoxy ]benzoate; mp. 130.1° C. (comp. 1).

Workup

  1. temperatureAfter cooling
  2. customthe layers were separated
  3. customThe organic layer was dried
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified by column chromatography over silica gel using
  7. additiona mixture of trichloromethane and ethanol (99:1 by volume) as eluent
  8. customThe pure fractions were collected
  9. customthe eluent was evaporated
  10. customThe residue was crystallized from a mixture of 2,2'-oxybixpropane and 2-propanone (75:25 by volume)
  11. filtrationThe precipitated product as filtered off
  12. customdried

Sources & evidence

ORD record
ord-42a8382b573b4ab484423d83d7dd51c1
Source dataset
uspto-grants-1993_07
Patent number
US05231184

Reaction notes

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