Hydrochloric Acid → 1-Phenyl-1,4-dihydrothiochromeno(4,3-c)pyrazole-3-carboxylic acid

HRID 373852Notes

Reaction equation

HRID 373852 reaction equation
[C:1]1([N:7]2[C:11]3[C:12]4[CH:19]=[CH:18][CH:17]=[CH:16][C:13]=4[S:14][CH2:15][C:10]=3[C:9]([C:20]([O:22]CC)=[O:21])=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[K+].Cl>C(O)C>[C:1]1([N:7]2[C:11]3[C:12]4[CH:19]=[CH:18][CH:17]=[CH:16][C:13]=4[S:14][CH2:15][C:10]=3[C:9]([C:20]([OH:22])=[O:21])=[N:8]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 14653456HCID 14653456, compound

Product 1

HCID 3309831-Phenyl-1,4-dihydrothiochromeno(4,3-c)pyrazole-3-carboxylic acidYield 88.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

1,4-dihydro-1-phenyl-[1]-benzothiopyrano[4,3-c]pyrazole-3-carboxylic acid, ethyl ester (3,2 g) is heated with 1% KOH solution in ethanol (80 ml) under reflux for 30 minutes. The reaction mixture is diluted with ice water and acidified to pH 3 with 37% HCl. The precipitate is filtered, washed with water and dried in vacuo at 50° C. to give 1,4-dihydro-1-phenyl-[1]-benzothiopyrano[4,3-c]pyrazol-3-carboxylic acid (2.6 g) which is reacted with thionyl chloride (0.9 ml) in dioxane (50 ml) under reflux for 2 hours. After cooling, the solution is evaporated to dryness in vacuo to give 1,4-dihydro-1-phenyl-[1]-benzothiopyrano[4,3-c]pyrazol-3-carbonyl chloride as a crystalline residue. The crude product is dissolved in anhydrous dioxane (35 ml) and reacted for 1 hour under stirring at room temperature with the carbanion obtained by treatment of N-cyanoacetylglycine, methyl ester (1.44 ng) with 50% sodium hydride (0.54 g) in anhydrous dimethylformamide/dioxane 1:1 (30 ml) at room temperature. The reaction mixture is then diluted with ice water and acidified to pH 2 with N HCl. The precipitate is filtered and dissolved in ethyl acetate, then the organic solution is washed with N HCl and then with water until neutral. Evaporation to dryness yields a residue which is purified over a Flash column using chloroform/methanol/30% NH4OH 80:20:0.5 as eluent. Final treatment with acetone of the purified fractions gives 1.65 g of N-[2-cyano-3-(1,4-dihydro-1-phenyl-[1]-benzothiopyrano[4,3-c]pyrazol-3-yl)-3-oxopropanoyl]-glycine,methyl ester, m.p. 208°-210° C., NMR (CDCl3) δppm: 3.81(s) (3H, --COOCH3), 4.18 (d) (2H, --CONHCH2 --), 4.21(s) (2H, --S--CH2 --), 6.82(t) (1H, --CONHCH2), 6.85-7.7 (m) (9H, phenyl protons), 16.32(s) (1H, --OH).

Workup

  1. temperatureunder reflux for 30 minutes
  2. filtrationThe precipitate is filtered
  3. washwashed with water
  4. customdried in vacuo at 50° C.

Sources & evidence

ORD record
ord-81dcb2baa1cc448898233d7e08df8d8e
Source dataset
uspto-grants-1992_11
Patent number
US05166152

Reaction notes

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