Citric Acid → HCID 15485784, compound

HRID 1292308Notes

Reaction equation

HRID 1292308 reaction equation
[NH2:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([N:11]2[C:15]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)=[CH:14][C:13]([C:23](O)=[O:24])=[N:12]2)=[CH:7][CH:6]=1)(=[O:4])=[O:3].O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[Cl:49][C:50]1[CH:51]=[C:52]([CH:54]=[CH:55][CH:56]=1)[NH2:53].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C)C=O>[Cl:49][C:50]1[CH:51]=[C:52]([NH:53][C:23]([C:13]2[CH:14]=[C:15]([C:16]3[CH:17]=[CH:18][C:19]([F:22])=[CH:20][CH:21]=3)[N:11]([C:8]3[CH:7]=[CH:6][C:5]([S:2]([NH2:1])(=[O:4])=[O:3])=[CH:10][CH:9]=3)[N:12]=2)=[O:24])[CH:54]=[CH:55][CH:56]=1

Participants

7

Reactant 5

HCID 311Citric AcidHCID 79323-ChloroanilineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 10666285HCID 10666285, compound

Product 1

HCID 15485784HCID 15485784, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A 100 mL one-neck round-bottom flask, equipped with provisions for magnetic stirring, was charged with [1-(4-aminosulfonylphenyl)-5-(4-fluorophenyl)-1H-pyrazol-3-yl]carboxylic acid from Step 3 (0.500 g, 1.38 mmol), 1-hydroxybenzotriazole hydrate (0.206 g, 1.522 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.318 g, 1.66 mmol) and N,N-dimethylformamide (30 mL). The solution was stirred at room temperature for forty minutes, then 3-chloroaniline (0.154 mL, 1.453 mmol) was added. The reaction was held at room temperature for sixteen hours, then poured into an aqueous solution of citric acid (5%, 100 mL). The aqueous solution was extracted with ethyl acetate (2×60 mL), and the combined organic solutions were washed with aqueous citric acid (60 mL), saturated sodium bicarbonate solution (2×60 mL) and 50% saturated sodium chloride solution (2×60 mL). The organic solution was dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to an oil. Trituration with 20 mL of dichloromethane yielded, upon filtration and drying, 0.439 g (67%) of N-(3-chlorophenyl)-[1-(4-aminosulfonylphenyl)-5-(4-fluorophenyl)-1H-pyrazol-3-yl]carboxamide as a white solid: mp 207°-212° C.; 1 H NMR (CDCl3 /CD3OD/300 MHz) 8.90 (s, 1H), 7.86 (d, J=8.66 Hz, 2H), 7.79 (t, J=2.01 Hz, 1H), 7.46 (dd, J=7.05 Hz, J=2.01 Hz, 1H), 7.33 (d, J=8.86 Hz, 2H), 7.21-7.11 (m, 3H), 7.02-6.94 (m, 4H). 19F NMR (CDCl3 /CD3OD/282.2 MHz): -111.38(m). Mass spectrum, MH+=470. Anal. Calc'd for C22H16N4O3ClFS: C, 56.11; H, 3.42; N, 11.90; Cl, 6.81; S, 7.53. Found: C, 55.95; H, 3.50; N, 11.85; Cl, 6.82; S, 7.50.

Workup

  1. customA 100 mL one-neck round-bottom flask, equipped with provisions for magnetic stirring
  2. waitThe reaction was held at room temperature for sixteen hours
  3. extractionThe aqueous solution was extracted with ethyl acetate (2×60 mL)
  4. washthe combined organic solutions were washed with aqueous citric acid (60 mL), saturated sodium bicarbonate solution (2×60 mL) and 50% saturated sodium chloride solution (2×60 mL)
  5. dry with materialThe organic solution was dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo to an oil
  8. customTrituration with 20 mL of dichloromethane yielded, upon filtration
  9. customdrying

Sources & evidence

ORD record
ord-473c5d50dc8c46588ce1d4d1b76b4a16
Source dataset
uspto-grants-1998_05
Patent number
US05756529

Reaction notes

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