Dimethylformamide → HCID 135982074, compound

HRID 1161535Notes

Reaction equation

HRID 1161535 reaction equation
C(N(CC)CC)C.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O.FC(F)(F)C(O)=O.C([O:32][C:33]([C:35]1[CH:36]=[N:37][NH:38][C:39]=1[N:40]1[C:44](=[O:45])[NH:43][C:42]([CH:46]([NH:61][C:62]2[CH:67]=[CH:66][C:65]([C:68](=[NH:70])[NH2:69])=[CH:64][CH:63]=2)[C:47]2[CH:52]=[C:51]([O:53][CH3:54])[CH:50]=[C:49]([O:55][CH2:56][CH2:57][CH2:58][OH:59])[C:48]=2[F:60])=[N:41]1)=[O:34])C.CN(C=O)C>CN(C)C1C=CN=CC=1.C(#N)C>[C:68]([C:65]1[CH:64]=[CH:63][C:62]([NH:61][CH:46]([C:47]2[CH:52]=[C:51]([O:53][CH3:54])[CH:50]=[C:49]([O:55][CH2:56][CH2:57][CH2:58][OH:59])[C:48]=2[F:60])[C:42]2[NH:43][C:44](=[O:45])[N:40]([C:39]3[NH:38][N:37]=[CH:36][C:35]=3[C:33]([OH:34])=[O:32])[N:41]=2)=[CH:67][CH:66]=1)(=[NH:69])[NH2:70]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 90495Di-tert-butyl dicarbonateHCID 136359401HCID 136359401, compound

Product 1

HCID 135982074HCID 135982074, compoundYield 36.7%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6342AcetonitrileSolvent

Procedure

After adding 38 μl of triethylamine, 0.3 mg of 4-dimethylaminopyridine and 46 mg of di-t-butyl dicarbonate to a solution of 55 mg of 5-(3-{(4-carbamimidoylphenylamino)-[2-fluoro-3-(3-hydroxypropoxy)-5-methoxyphenyl]methyl}-5-oxo-4,5-dihydro-[1,2,4]triazol-1-yl)-1H-pyrazole-4-carboxylic acid ethyl ester trifluoroacetate in 6 ml of an acetonitrile:DMF=2:1 mixed solvent, the mixture was stirred at room temperature for 15 hours. The solvent was removed under reduced pressure, and then 1 ml of methanol and 1 ml of a 1N aqueous sodium hydroxide solution were added and the mixture was stirred at room temperature for 8 hours. After adding 5 ml of a methanol:water:acetic acid=1:1:1 mixed solvent to the reaction mixture, it was stirred and heated at 50° C. for 15 hours. The mixture was cooled and then directly purified by reverse-phase high performance liquid chromatography (acetonitrile-water, 0.1% acetic acid) to give 16 mg of the title compound.

Workup

  1. customThe solvent was removed under reduced pressure
  2. addition1 ml of methanol and 1 ml of a 1N aqueous sodium hydroxide solution were added
  3. additionAfter adding 5 ml of a methanol
  4. stirringwater:acetic acid=1:1:1 mixed solvent to the reaction mixture, it was stirred
  5. temperatureheated at 50° C. for 15 hours
  6. temperatureThe mixture was cooled
  7. customdirectly purified by reverse-phase high performance liquid chromatography (acetonitrile-water, 0.1% acetic acid)

Sources & evidence

ORD record
ord-ef24095527a648d0b0c01e6d6b0f5564
Source dataset
uspto-grants-2010_10
Patent number
US07816522B2

Reaction notes

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