Citric Acid → HCID 15485784, compound

HRID 1274285Notes

Reaction equation

HRID 1274285 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 was 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.; 1H 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. customyielded, upon filtration
  9. customdrying

Sources & evidence

ORD record
ord-ff3857239e294eb28f8b1d8dc24a9fce
Source dataset
uspto-grants-2000_12
Patent number
US06156781

Reaction notes

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