Sodium Hydroxide → Pyrazolopyrimidinone

HRID 2367654Notes

Reaction equation

CCC[C:4]1[C:5]2[N:14]=[C:13](C3C=C(S(N4CCN(C)CC4)(=O)=O)C=CC=3OCC)[NH:12][C:10](=O)[C:6]=2[N:7](C)[N:8]=1.[OH-:34].[Na+]>>[N:7]1[C:6]2[CH:10]=[N:12][CH:13]=[N:14][C:5]=2[C:4](=[O:34])[N:8]=1

Participants

Reactant 2

HCID 14798Sodium Hydroxide

HCID 135398744Sildenafil

Product 1

HCID 53630237PyrazolopyrimidinoneYield 77%

Procedure

Drug preparation: Sildenafil was synthesized in 6 steps according to reported procedures (Terrett et al., 1996) (U.S. Pat. No. 5,346,901.1994). Briefly, commercially available 2-ethoxybenzoic acid was converted to 2-ethoxybenzoyl chloride with thionyl chloride. Reaction of 2-ethoxybenzoyl chloride with 4-amino-1-methyl-3-N-propylpyrazole-5-carboxamide yielded the amide in 90% yield. Cyclization of the amide using NaOH afforded pyrazolopyrimidinone in 77% yield. Chlorosulfonylation of the pyrazolopyrimidinone in chlorosulfonic acid, followed by reaction with N-methylpiperazine provided sildenafil in 90% yield. Tadalafil was also synthesized according to reported procedures (Daugan et al., 2003b). Briefly, D-tryptophan methyl ester reacted with piperonal under Pictet-Spengler reaction condition (TFA/CH2Cl2/MeOH) and the resulting product condensed with chloroacetyl chloride to provide acylated intermediate. Reaction of the intermediate with N-methyl amine provided tadalafil. Tadalafil was diluted in 0.1% DMSO.

Sources & evidence

ORD record: ord-bd5fbe6d5fb04a919beadf9db86853b9
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08697875B2

Reaction notes

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