Ethyl orthoformate → 4-[4-(2,3-Difluoro-phenyl)-4H-[1,2,4]triazol-3-yl]-1H-pyrrole-2-carboxylic acid

HRID 2249520Notes

Reaction equation

HRID 2249520 reaction equation
C[O:2][C:3]([C:5]1[N:6](S(C)(=O)=O)[CH:7]=[C:8]([C:10](=[N:20][NH2:21])[NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[C:13]=2[F:19])[CH:9]=1)=[O:4].[CH:26](OCC)(OCC)OCC.C([O-])(O)=O.[Na+]>C(O)=O>[F:19][C:13]1[C:14]([F:18])=[CH:15][CH:16]=[CH:17][C:12]=1[N:11]1[CH:26]=[N:21][N:20]=[C:10]1[C:8]1[CH:9]=[C:5]([C:3]([OH:2])=[O:4])[NH:6][CH:7]=1

Participants

5

Reactant 3

HCID 31214Ethyl orthoformateHCID 516892Sodium BicarbonateHCID 178498204HCID 178498204, compound

Product 1

HCID 1360762454-[4-(2,3-Difluoro-phenyl)-4H-[1,2,4]triazol-3-yl]-1H-pyrrole-2-carboxylic acid

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Procedure

A mixture of 4-[N-(2,3-difluoro-phenyl)-N′-amino-carbamimidoyl]-1-methanesulfonyl-1H-pyrrole-2-carboxylic acid methyl ester (200 mg, 0.54 mmol), CH(OEt)3 (4 mL), and HCOOH (0.8 mL) was stirred at room temperature for 2 hours and poured into 50 mL of aqueous NaHCO3 solution. The aqueous mixture was extracted with EtOAc and the combined organic layers were dried over Na2SO4, filtered, and evaporated. The crude material was used for the next step without further purification. This crude product was dissolved in MeOH (5 mL) then 6N NaOH aqeous solution was added (1 mL) and the mixture was heated at 50° C. for 3 hours. The solvent was evaporated and the residue was acidified with 6N HCl to pH 3. The white precipitate was collected by filtration and washed with water. The crude product (150 mg, 96%) was dried on the pump for the next reaction. 1H NMR (500 MHz, DMSO-d6) δ12.61 (s, br, 1H), 12.20 (s, 1H), 8.78 (s, 1H), 7.75 (m, 1H), 7.55 (m, 1H), 7.47 (m, 1H), 6.96 (s, 1H), 6.58 (s, 1H) ppm. MS (ES+): m/e=291.1 (M+H); LC/Method A/2.46 min.

Workup

  1. extractionThe aqueous mixture was extracted with EtOAc
  2. dry with materialthe combined organic layers were dried over Na2SO4
  3. filtrationfiltered
  4. customevaporated
  5. customThe crude material was used for the next step without further purification
  6. dissolutionThis crude product was dissolved in MeOH (5 mL)
  7. addition6N NaOH aqeous solution was added (1 mL)
  8. temperaturethe mixture was heated at 50° C. for 3 hours
  9. customThe solvent was evaporated
  10. filtrationThe white precipitate was collected by filtration
  11. washwashed with water
  12. dry with materialThe crude product (150 mg, 96%) was dried on the pump for the next reaction
  13. customLC/Method A/2.46 min.

Sources & evidence

ORD record
ord-ff5e3a0f1c1d45df9a35d5612a72a6a0
Source dataset
uspto-grants-2008_01
Patent number
US07314885B2

Reaction notes

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