Triethylamine → 5-{3-[(4-carbamimidoylphenylamino)-(2-fluoro-4,5-dimethoxyphenyl)methyl]-5-oxo-4,5-dihydro-[1,2,4]triazol-1-yl}-1H-pyrazole-4-carboxylic acid acetate

HRID 1161507Notes

Reaction equation

HRID 1161507 reaction equation
C(N(CC)CC)C.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O.[C:23]([OH:26])(=[O:25])[CH3:24].C([O:29][C:30]([C:32]1[CH:33]=[N:34][NH:35][C:36]=1[N:37]1[C:41](=[O:42])[NH:40][C:39]([CH:43]([NH:55][C:56]2[CH:61]=[CH:60][C:59]([C:62](=[NH:64])[NH2:63])=[CH:58][CH:57]=2)[C:44]2[CH:49]=[C:48]([O:50][CH3:51])[C:47]([O:52][CH3:53])=[CH:46][C:45]=2[F:54])=[N:38]1)=[O:31])C>CN(C)C1C=CN=CC=1.C(#N)C>[C:23]([OH:26])(=[O:25])[CH3:24].[C:62]([C:59]1[CH:58]=[CH:57][C:56]([NH:55][CH:43]([C:44]2[CH:49]=[C:48]([O:50][CH3:51])[C:47]([O:52][CH3:53])=[CH:46][C:45]=2[F:54])[C:39]2[NH:40][C:41](=[O:42])[N:37]([C:36]3[NH:35][N:34]=[CH:33][C:32]=3[C:30]([OH:31])=[O:29])[N:38]=2)=[CH:61][CH:60]=1)(=[NH:63])[NH2:64]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 90495Di-tert-butyl dicarbonateHCID 1363892695-{3-[(4-carbamimidoylphenylamino)-(2-fluoro-4,5-dimethoxyphenyl)methyl]-5-oxo-4,5-dihydro-[1,2,4]triazol-1-yl}-1H-pyrazole-4-carboxylic acid ethyl ester acetate

Product 1

HCID 1363892705-{3-[(4-carbamimidoylphenylamino)-(2-fluoro-4,5-dimethoxyphenyl)methyl]-5-oxo-4,5-dihydro-[1,2,4]triazol-1-yl}-1H-pyrazole-4-carboxylic acid acetateYield 52.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6342AcetonitrileSolvent

Procedure

After adding 0.056 ml of triethylamine, 0.0015 g of 4-dimethylaminopyridine and 71 mg of di-t-butyl dicarbonate to a solution of 0.068 g of 5-{3-[(4-carbamimidoylphenylamino)-(2-fluoro-4,5-dimethoxyphenyl)methyl]-5-oxo-4,5-dihydro-[1,2,4]triazol-1-yl}-1H-pyrazole-4-carboxylic acid ethyl ester acetate in 4 ml of acetonitrile, the mixture was stirred at room temperature for 15 minutes. The solvent was removed under reduced pressure, and then 1 ml of methanol and 1 ml of a 5N aqueous solution of sodium hydroxide were added and the mixture was further stirred at room temperature for 6 hours. Next, 2 ml of acetic acid, 1 ml of water and 1 ml of methanol were added to the reaction mixture, which was then stirred and heated at 50° C. for 15 hours. After cooling, purification was performed by reverse-phase high performance liquid chromatography (acetonitrile-water, 0.1% acetic acid) to give 0.034 g of the title compound.

Workup

  1. customThe solvent was removed under reduced pressure
  2. addition1 ml of methanol and 1 ml of a 5N aqueous solution of sodium hydroxide were added
  3. stirringthe mixture was further stirred at room temperature for 6 hours
  4. additionNext, 2 ml of acetic acid, 1 ml of water and 1 ml of methanol were added to the reaction mixture, which
  5. stirringwas then stirred
  6. temperatureheated at 50° C. for 15 hours
  7. temperatureAfter cooling
  8. custompurification

Sources & evidence

ORD record
ord-2b119818df294af6a708ab4c4e5b8922
Source dataset
uspto-grants-2010_10
Patent number
US07816522B2

Reaction notes

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