Methanol → 4-{3-[(4-Carbamimidoylphenylamino)-(5-fluoro-8-methoxy-2,3-dihydrobenzo[1,4]dioxin-6-yl)methyl]-5-oxo-4,5-dihydro-[1,2,4]triazol-1-yl}thiazole-5-carboxylic acid

HRID 1161553Notes

Reaction equation

HRID 1161553 reaction equation
CO.C([O:5][C:6]([C:8]1[S:12][CH:11]=[N:10][C:9]=1[N:13]1[C:17](=[O:18])[NH:16][C:15]([CH:19]([C:36]2[CH:45]=[C:44]([O:46][CH3:47])[C:39]3[O:40][CH2:41][CH2:42][O:43][C:38]=3[C:37]=2[F:48])[NH:20][C:21]2[CH:26]=[CH:25][C:24]([C:27]3[N:31]=C(C(F)(F)F)O[N:28]=3)=[CH:23][CH:22]=2)=[N:14]1)=[O:7])C.[OH-].[Na+]>[Fe].C(O)(=O)C>[C:27]([C:24]1[CH:25]=[CH:26][C:21]([NH:20][CH:19]([C:36]2[CH:45]=[C:44]([O:46][CH3:47])[C:39]3[O:40][CH2:41][CH2:42][O:43][C:38]=3[C:37]=2[F:48])[C:15]2[NH:16][C:17](=[O:18])[N:13]([C:9]3[N:10]=[CH:11][S:12][C:8]=3[C:6]([OH:7])=[O:5])[N:14]=2)=[CH:22][CH:23]=1)(=[NH:28])[NH2:31]

Participants

6

Reactant 3

HCID 887Methanol2×HCID 14798Sodium HydroxideHCID 1359821604-(3-{(5-Fluoro-8-methoxy-2,3-dihydrobenzo[1,4]dioxin-6-yl)-[4-(5-trifluoromethyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-5-oxo-4,5-dihydro-[1,2,4]triazol-1-yl)thiazole-5-carboxylic acid ethyl ester

Product 1

HCID 1359821074-{3-[(4-Carbamimidoylphenylamino)-(5-fluoro-8-methoxy-2,3-dihydrobenzo[1,4]dioxin-6-yl)methyl]-5-oxo-4,5-dihydro-[1,2,4]triazol-1-yl}thiazole-5-carboxylic acid

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 176Acetic AcidSolvent

Procedure

To 2 ml of a methanol solution containing 57 mg of 4-(3-{(5-fluoro-8-methoxy-2,3-dihydrobenzo[1,4]dioxin-6-yl)-[4-(5-trifluoromethyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-5-oxo-4,5-dihydro-[1,2,4]triazol-1-yl)thiazole-5-carboxylic acid ethyl ester, 0.2 ml of a 5 N sodium hydroxide aqueous solution was added. The resulting mixture was stirred at room temperature for 18 hours, and then 2 ml of methanol, 2 ml of acetic acid, and 38 mg of iron powder were added thereto. The mixture was stirred at 60° C. for 18 hours and then at 65° C. for 6 hours, under a nitrogen atmosphere. After cooling, the reaction mixture was purified by reverse-phase high performance liquid chromatography (acetonitrile-water, 0.1% acetic acid) to give 4-{3-[(4-carbamimidoylphenylamino)-(5-fluoro-8-methoxy-2,3-dihydrobenzo[1,4]dioxin-6-yl)methyl]-5-oxo-4,5-dihydro-[1,2,4]triazol-1-yl}thiazole-5-carboxylic acid.

Workup

  1. additionwas added
  2. stirringThe mixture was stirred at 60° C. for 18 hours
  3. waitat 65° C. for 6 hours
  4. temperatureAfter cooling
  5. customthe reaction mixture was purified by reverse-phase high performance liquid chromatography (acetonitrile-water, 0.1% acetic acid)

Sources & evidence

ORD record
ord-dbb6abbe1d444ef28233fc8623ccef9d
Source dataset
uspto-grants-2010_10
Patent number
US07816522B2

Reaction notes

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