Formic Acid → HCID 58179594, compound

HRID 1518501Notes

Reaction equation

HRID 1518501 reaction equation
[NH2:1][C:2]1[C:3]([C:8]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[C:13]=2[F:19])=[N:9][NH2:10])=[N:4][CH:5]=[CH:6][N:7]=1.[CH:20](O)=O.C([O-])(O)=O.[Na+].[OH-].[Na+]>C(OCC)(OCC)OCC>[F:19][C:13]1[C:14]([F:18])=[CH:15][CH:16]=[CH:17][C:12]=1[N:11]1[CH:20]=[N:10][N:9]=[C:8]1[C:3]1[C:2]([NH2:1])=[N:7][CH:6]=[CH:5][N:4]=1

Participants

6

Reactant 4

HCID 284Formic AcidHCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 178514391HCID 178514391, compound

Product 1

HCID 58179594HCID 58179594, compoundYield 92%

Reagents, catalysts & solvents 1

HCID 31214Ethyl orthoformateSolvent

Procedure

3-Amino-N-(2,3-difluorophenyl)-N′-aminopyrazine-2-carboxamidine (500 mg, 1.89 mmol) was dissolved in CH(OEt)3 (20 mL) and HCOOH (5 mL) was added slowly at RT. The solution was kept at RT for 30 min and carefully neutralized with saturated NaHCO3 and 6N NaOH until a pH of 10 was achieved. The resulting mixture was extracted with ethyl acetate. The combined organic layers were dried over MgSO4 and evaporated to produce 3-(4-(2,3-Difluorophenyl)-4H-1,2,4-triazol-3-yl)pyrazin-2-amine as yellow solid (480 mg, 92%). A small amount of the crude product was purified by HPLC for characterization and the remainder used directly in the next reaction without further purification. LC-MS m/e=274.8 (M+H). Using the same procedure, 3-(4-(2,3-dichlorophenyl)-4H-1,2,4-triazol-3-yl)pyrazin-2-amine, 3-(4-(3-chloro-2-fluorophenyl)-4H-1,2,4-triazol-3-yl)pyrazin-2-amine, 3-(4-(2,3-difluorophenyl)-4H-1,2,4-triazol-3-yl)pyridin-2-amine, 3-(4-(2,3-dichlorophenyl)-4H-1,2,4-triazol-3-yl)pyridin-2-amine, and 3-(4-(3-chloro-2-fluorophenyl)-4H-1,2,4-triazol-3-yl)pyridin-2-amine can be produced from 3-amino-N-(2,3-dichlorophenyl)-N′-aminopyrazine-2-carboxamidine, 3-amino-N-(3-chloro-2-fluorophenyl)-N′-aminopyrazine-2-carboxamidine, 2-amino-N-(2,3-difluorophenyl)-N′-aminopyridine-3-carboxamidine, 2-amino-N-(2,3-dichlorophenyl)-N′-aminopyridine-3-carboxamidine, and 2-amino-N-(3-chloro-2-fluorophenyl)-N′-aminopyridine-3-carboxamidine, respectively.

Workup

  1. extractionThe resulting mixture was extracted with ethyl acetate
  2. dry with materialThe combined organic layers were dried over MgSO4
  3. customevaporated

Sources & evidence

ORD record
ord-e541ff4215e64f2d8224bb3dc06b6dd4
Source dataset
uspto-grants-2012_07
Patent number
US08232406B2

Reaction notes

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