Water → HCID 19699076, compound

HRID 863044Notes

Reaction equation

HRID 863044 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].C(N(CC)CC)C.[F:31][C:32]1[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][C:33]=1[C:34](Cl)=[O:35].O>C(Cl)Cl>[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:34](=[O:35])[C:33]4[CH:37]=[C:38]([Cl:41])[CH:39]=[CH:40][C:32]=4[F:31])=[CH:22][C:2]=3[Cl:1])=[O:5])[CH2:12][CH2:11][C:10]=2[CH:13]=[N:14]1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 27736045-Chloro-2-fluorobenzoyl chlorideHCID 19699078HCID 19699078, compound

Product 1

HCID 19699076HCID 19699076, compoundYield 129.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

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 under argon is added 417 μl of triethylamine followed by a solution of 482 mg of 2-fluoro-5-chlorobenzoyl 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 650 mg of the desired product as a solid residue. To a solution of 500 mg of the preceding compound in 4 ml methanol and 4 ml of tetrahydrofuran is added 1.51 ml of 1N NaOH. The reactants are stirred at room temperature for 18 hours. The reaction mixture is neutralized with 1N HCl and evaporated in vacuo to a residue which is diluted with 50 ml of chloroform and washed with water, brine and dried (Na2SO4). The organic layer is passed through a pad of hydrous magnesium silicate. The filtrate is evaporated in vacuo to a residue which is crystallized from ethyl acetate containing ethyl alcohol. The collected solid is dried to give 215 mg of the desired product as an off white solid, m.p. 282°-288° 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

Sources & evidence

ORD record
ord-214078ae580d425ebcee5458d12865f5
Source dataset
uspto-grants-1998_02
Patent number
US05719278

Reaction notes

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