Hydrochloric Acid → HCID 22921576, compound

HRID 2258614Notes

Reaction equation

HRID 2258614 reaction equation
C[O-].[Na+].[NH2:4][C:5]([C:12]([F:15])([F:14])[F:13])=[CH:6][C:7]([O:9]CC)=O.[CH2:16]([N:19]1[C:23]2[CH:24]=[C:25]([NH:29][C:30](OCC)=[O:31])[C:26]([F:28])=[CH:27][C:22]=2[N:21]=[C:20]1[C:35]([F:38])([F:37])[F:36])[C:17]#[CH:18].N12CCCN=C1CCCCC2.Cl>CN(C)C=O>[CH2:16]([N:19]1[C:23]2[CH:24]=[C:25]([N:29]3[C:7](=[O:9])[CH:6]=[C:5]([C:12]([F:13])([F:14])[F:15])[NH:4][C:30]3=[O:31])[C:26]([F:28])=[CH:27][C:22]=2[N:21]=[C:20]1[C:35]([F:37])([F:38])[F:36])[C:17]#[CH:18]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 136209Ethyl 3-amino-4,4,4-trifluoro-2-butenoateHCID 10942334Sodium MethoxideHCID 22921551HCID 22921551, compound

Product 1

HCID 22921576HCID 22921576, compoundYield 28.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

Under a nitrogen atmosphere, a stirred solution of 0.4 gram (0.005 mole) of sodium methoxide in 5 mL of N,N-dimethylformamide was cooled to about 0°-5° C., and 1.8 grams (0.005 mole) of ethyl 3-amino-4,4,4-trifluoro-2-butenoate in 15 mL of N,N-dimethylformamide was added dropwise. Upon completion of the addition, the reaction mixture was allowed to warm to ambient temperature where it stirred for 30 minutes. After this time, the reaction mixture was again cooled, and a solution of 1.8 grams (0.005 mole) of 1-(2-propyn-1-yl)-2-trifluoromethyl-5-fluoro-6-ethoxycarbonylaminobenzimidazole in 20 mL of N,N-dimethylformamide was added dropwise. The reaction mixture was heated to 110° C., and 0.24 mL (catalyst) of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) was added in one portion. Upon completion of the addition, the reaction mixture was heated to about 130° C., where it stirred for about 3.5 hours. The reaction mixture was then allowed to cool to ambient temperature as it stirred for about 72 hours, after which the reaction mixture was poured into ice-cold aqueous 3N hydrochloric acid. The resultant precipitate was collected by filtration and dried, yielding 0.6 gram of 3-[1-(2-propyn-1-yl)-2-trifluoromethyl-5-fluorobenzimidazol-6-yl]-6-trifluoromethyluracil. The NMR spectrum was consistent with the proposed structure.

Workup

  1. additionUpon completion of the addition
  2. temperatureAfter this time, the reaction mixture was again cooled
  3. temperatureThe reaction mixture was heated to 110° C.
  4. additionUpon completion of the addition
  5. temperaturethe reaction mixture was heated to about 130° C.
  6. stirringwhere it stirred for about 3.5 hours
  7. temperatureto cool to ambient temperature as it
  8. stirringstirred for about 72 hours
  9. filtrationThe resultant precipitate was collected by filtration
  10. customdried

Sources & evidence

ORD record
ord-a36b8ade948e411aa15985bbce29742c
Source dataset
uspto-grants-1997_08
Patent number
US05661108

Reaction notes

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