Citric Acid → Sildenafil Citrate

HRID 1435823Notes

Reaction equation

HRID 1435823 reaction equation
[CH3:1][N:2]1[C:10]2[C:9](=[O:11])[N:8]=[C:7]([C:12]3[C:13](C4C=CC(OCC)=CC=4)=[C:14]([S:18](Cl)(=[O:20])=[O:19])[CH:15]=[CH:16][CH:17]=3)[NH:6][C:5]=2[C:4]([CH2:31][CH2:32][CH3:33])=[N:3]1.[OH-].[Na+].[CH3:36][N:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1.[C:43]([OH:55])(=[O:54])[CH2:44][C:45]([CH2:50][C:51]([OH:53])=[O:52])([C:47]([OH:49])=[O:48])[OH:46]>CC(C)=O>[CH3:33][CH2:32][CH2:31][C:4]1[C:5]2[N:6]=[C:7]([C:12]3[CH:13]=[C:14]([S:18]([N:40]4[CH2:41][CH2:42][N:37]([CH3:36])[CH2:38][CH2:39]4)(=[O:19])=[O:20])[CH:15]=[CH:16][C:17]=3[O:46][CH2:45][CH3:44])[NH:8][C:9](=[O:11])[C:10]=2[N:2]([CH3:1])[N:3]=1.[CH2:50]([C:45]([OH:46])([C:47]([OH:49])=[O:48])[CH2:44][C:43]([OH:55])=[O:54])[C:51]([OH:53])=[O:52]

Participants

6

Reactant 4

HCID 311Citric AcidHCID 14798Sodium HydroxideHCID 531671-MethylpiperazineHCID 178440326HCID 178440326, compound

Product 1

HCID 135413523Sildenafil CitrateYield 72%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent2×

Procedure

In a 3-necked flask, 3-(4,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo(4,3-d)pyrimidin-5-yl)-(4-ethoxyphenyl)benzene sulfonyl chloride (10 g, 0.024 mol) was mixed with acetone (100 ml) and NaOH (0.974 g, 47%) at room temperature. N-methyl piperazine (2.68 g, 0.027 mol) was added dropwise to the mixture. Thereafter, the reaction was stirred for 45 mm, additional acetone (100 ml) was added, and then the mixture was heated to reflux. Citric acid (5 g, 0.024 mol) was added, and a white precipitate appeared immediately. The reaction was maintained at reflux for one hour and then allowed to cool to room temperature over 3 hours. The precipitate was collected by filtration, and dried at 50° C. under 10 mm Hg to give pure sildenafil citrate in 72% yield.

Workup

  1. additionwas added
  2. temperaturethe mixture was heated to reflux
  3. temperatureThe reaction was maintained
  4. temperatureat reflux for one hour
  5. filtrationThe precipitate was collected by filtration
  6. customdried at 50° C. under 10 mm Hg

Sources & evidence

ORD record
ord-fd5e34d2acb1432293eade7ac49505ee
Source dataset
uspto-grants-2009_11
Patent number
US07618976B2

Reaction notes

Loading…