Pyridine-4-amidine hydrochloride → HCID 178419092, compound

HRID 1422202Notes

Reaction equation

HRID 1422202 reaction equation
C(O[C:4](=[O:20])[CH:5]([O:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[O:18][CH3:19])[C:6]([O:8]CC)=O)C.Cl.[C:22]([C:25]1[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=1)(=[NH:24])[NH2:23]>[Na].CO>[CH3:19][O:18][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[O:11][C:5]1[C:4]([OH:20])=[N:23][C:22]([C:25]2[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=2)=[N:24][C:6]=1[OH:8]

Participants

5

Reactant 2

HCID 2776844Pyridine-4-amidine hydrochlorideHCID 11140560Diethyl (2-methoxyphenoxy)propanedioate

Product 1

HCID 178419092HCID 178419092, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 5360545SodiumSolvent

Procedure

Diethyl-(2-methoxy-phenoxy)malonate is dissolved in a solution of sodium in methanol. Thereafter 4-amidino-pyridine hydrochloride is added to obtain 5-(2-methoxy-phenoxy)-2-(pyridin-4-yl)-pyrimidin-4,6-diol (or a tautomeric derivative). This compound is heated with phosphorus oxychloride to yield 4,6-dichloro-5-(2-methoxy-phenoxy)-2-pyridin-4-yl)-pyrimidine which is boiled with peracetic acid to obtain 4-[4,6-dichloro-5-(2-methoxy-phenoxy)-pyrimidin-2-yl]-pyridine-1-oxide. By reaction of this compound with 5-isopropyl-pyridine-2-sulfonamide potassium there is obtained 5-isopropyl-pyridine-2-sulfonic acid 6-chloro-5-(2-methoxy-phenoxy)-2-(1-oxy-pyridin-4-yl)-pyrimidin-4-yl amide which is added as a solution in dimethoxyethane to a solution of sodium in ethylene glycol. 5-Isopropyl-pyridine-2-sulfonic acid 6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2-(1-oxy-pyridin-4-yl)-pyrimidin-4-yl amide is obtained which is heated with trimethylsilylcyanide and triethylamine in acetonitrile to obtain 5-isopropyl-pyridine-2-sulphonic acid 2-(2-cyano-pyridin-4-yl)-6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-pyrimidin-4-yl-amide. This is then heated with ammonium chloride and sodium azide in dimethyl formamide to yield 5-isopropyl-pyridine-2-sulfonic acid {6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2-[2-(1H-tetrazol-5-yl)-pyridin-4-yl]-pyrimidin-4-yl}-amide (see WO 96/19459).

Sources & evidence

ORD record
ord-76246026c5fe48c5960c4dbab24a1af4
Source dataset
uspto-grants-2000_06
Patent number
US06080866

Reaction notes

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