3-Pyridinecarbonyl chloride, hydrochloride (1:1) → HCID 20208703, compound

HRID 2413195Notes

Reaction equation

HRID 2413195 reaction equation
Cl.[C:2](Cl)(=[O:9])[C:3]1[CH:8]=[CH:7][CH:6]=[N:5][CH:4]=1.[CH2:11]([N:14]=[C:15]([NH2:29])[NH:16][C:17]1[CH:22]=[CH:21][N:20]=[C:19]([CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][NH2:28])[N:18]=1)[CH2:12][CH3:13]>CCO.C(N(CC)CC)C>[CH2:11]([N:14]=[C:15]([NH2:29])[NH:16][C:17]1[CH:22]=[CH:21][N:20]=[C:19]([CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][NH:28][C:2](=[O:9])[C:3]2[CH:8]=[CH:7][CH:6]=[N:5][CH:4]=2)[N:18]=1)[CH2:12][CH3:13]

Participants

5

Reactant 2

HCID 884383-Pyridinecarbonyl chloride, hydrochloride (1:1)HCID 53678275HCID 53678275, compound

Product 1

HCID 20208703HCID 20208703, compoundYield 5.4%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8471TriethylamineSolvent

Procedure

Nicotinoyl chloride hydrochloride (0.2 g.) was added at 0° to a stirred solution of 4-(2-propyl-guanidino)-2-(5-aminopentyl)pyrimidine (0.2 g.) in EtOH (5 ml.) and triethylamine (2 ml.). The mixture was stirred at room temperature for 16 hours and evaporated to dryness. The residue was partitioned between 2 N aqueous HCl and EtOAc and the aqueous phase was then basified with 10 N aqueous NaOH and extracted with EtOAc. The extract was dried (MgSO4) and evaporated to dryness. The residual gum was purified twice by preparative thin layer chromatography on Merck 60 F-254 plates using EtOAc/MeOH/aqueous ammonia (s.g. 0.88) 6:1:1 v/v/v as developing solvent. The appropriate zone of the chromatogram was extracted with MeOH/aqueous ammonia (s.g. 0.88) 10:1 v/v and the solvent was evaporated. The residual gum was dissolved in EtOAc, filtered and treated with an excess of a saturated solution of maleic acid in EtOAc. The precipitated gum was washed with EtOAc to give N-[5-(4-[2-propylguanidino]-pyrimid-2-yl)pentyl]nicotinamide (0.015 g.) as a straw coloured gum. The n.m.r. spectrum in d4MeOH using tetramethylsilane as standard included the following resonances (δ):1.0 (3H, triplet), 1.7 (8H, multiplet), 2.9 (2H, triplet), 3.6 (2H, triplet), 6.8 (1H, doublet), 7.6 (1H, multiplet), 8.3 (2H, multiplet) and 8.8 (2H, complex).

Workup

  1. customevaporated to dryness
  2. customThe residue was partitioned between 2 N aqueous HCl and EtOAc
  3. extractionextracted with EtOAc
  4. dry with materialThe extract was dried (MgSO4)
  5. customevaporated to dryness
  6. customThe residual gum was purified twice by preparative thin layer chromatography on Merck 60 F-254 plates
  7. extractionThe appropriate zone of the chromatogram was extracted with MeOH/aqueous ammonia (s.g. 0.88) 10:1 v/v
  8. customthe solvent was evaporated
  9. dissolutionThe residual gum was dissolved in EtOAc
  10. filtrationfiltered
  11. additiontreated with an excess of a saturated solution of maleic acid in EtOAc
  12. washThe precipitated gum was washed with EtOAc

Sources & evidence

ORD record
ord-9cd00a09a8e44c90bcde50cff2a6382d
Source dataset
uspto-grants-1985_01
Patent number
US04496571

Reaction notes

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