Hydrochloric Acid → HCID 9805201, compound

HRID 1733992Notes

Reaction equation

HRID 1733992 reaction equation
[Cl:1][C:2]1[CH:22]=[C:21]([NH2:23])[CH:20]=[CH:19][C:3]=1[C:4]([N:6]1[CH2:12][CH2:11][C:10]2[CH:13]=[N:14][NH:15][C:9]=2[C:8]2[S:16][CH:17]=[CH:18][C:7]1=2)=[O:5].[CH3:24][C:25]1[CH:33]=[CH:32][C:31]([F:34])=[CH:30][C:26]=1[C:27](Cl)=[O:28].[OH-].[Na+].Cl>C(Cl)Cl.CO.O1CCCC1.O.C(N(CC)CC)C>[NH:15]1[C:9]2[C:8]3[S:16][CH:17]=[CH:18][C:7]=3[N:6]([C:4]([C:3]3[CH:19]=[CH:20][C:21]([NH:23][C:27](=[O:28])[C:26]4[CH:30]=[C:31]([F:34])[CH:32]=[CH:33][C:25]=4[CH3:24])=[CH:22][C:2]=3[Cl:1])=[O:5])[CH2:12][CH2:11][C:10]=2[CH:13]=[N:14]1

Participants

10

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 27373835-Fluoro-2-methylbenzoyl chlorideHCID 19699078HCID 19699078, compound

Product 1

HCID 9805201HCID 9805201, compoundYield 57.1%

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent3×HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

To an ice bath cooled mixture of 345 mg of 6(2-chloro-4-aminobenzoyl)-1,4,5,6-tetrahydropyrazolo[3,4-d]thieno[3,2-b]azepine in 3.5 ml of methylene chloride is added 417 μl of triethylamine is added a solution of 432 mg of 2-methyl-5-fluorobenzoyl chloride in 1.5 ml of methylene chloride. The reaction mixture is stirred at room temperature for 18 hours under argon. An additional 40 ml of methylene chloride is added followed by 20 ml of water. The organic layer is washed with 20 ml each of 2N citric acid, 1M NaHCO3 and brine. The organic layer is dried (Na2SO4), filtered through hydrous magnesium silicate and the filtrate evaporated in vacuo to give a foam residue. To a solution of 800 mg of the preceding compound in 4 ml methanol and 4 ml of tetrahydrofuran is added 2.7 ml of 1N NaOH. The reactants are stirred at room temperature for 1.5 hours. The reaction mixture is neutralized with 1N HCl and evaporated in vacuo to a residue which is diluted with 50 ml of methylene chloride and water and then filtered. The collected solid is dried at 60° C. to give 275 mg of the desired product as an off-white solid, m.p. 310°-312° C.

Workup

  1. temperatureTo an ice bath cooled
  2. washThe organic layer is washed with 20 ml each of 2N citric acid, 1M NaHCO3 and brine
  3. dry with materialThe organic layer is dried (Na2SO4)
  4. filtrationfiltered through hydrous magnesium silicate
  5. customthe filtrate evaporated in vacuo
  6. customto give a foam residue
  7. stirringThe reactants are stirred at room temperature for 1.5 hours
  8. customevaporated in vacuo to a residue which
  9. additionis diluted with 50 ml of methylene chloride and water
  10. filtrationfiltered
  11. customThe collected solid is dried at 60° C.

Sources & evidence

ORD record
ord-6f2471cfa22d408fa34bc4d03686d607
Source dataset
uspto-grants-1996_07
Patent number
US05532235

Reaction notes

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