Sodium Carbonate → HCID 59631939, compound

HRID 2369035Notes

Reaction equation

HRID 2369035 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:9]=[C:8]([C:10]2[S:11][C:12](Br)=[CH:13][CH:14]=2)[N:7]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[Cl:22])[N:6]=1)=[O:4].[CH3:23][S:24]([C:27]1[CH:28]=[C:29](B(O)O)[CH:30]=[CH:31][CH:32]=1)(=[O:26])=[O:25].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[CH3:1][O:2][C:3]([C:5]1[CH:9]=[C:8]([C:10]2[S:11][C:12]([C:31]3[CH:30]=[CH:29][CH:28]=[C:27]([S:24]([CH3:23])(=[O:26])=[O:25])[CH:32]=3)=[CH:13][CH:14]=2)[N:7]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[Cl:22])[N:6]=1)=[O:4]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27735423-(Methylsulfonyl)phenylboronic acidHCID 59633025HCID 59633025, compound

Product 1

HCID 59631939HCID 59631939, compoundYield 50.7%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 5-(5-bromo-thiophen-2-yl)-1-(2-chloro-phenyl)-1H-pyrazole-3-carboxylic acid methyl ester (8.0 g, 20 mmol), 3-methylsulfonylphenylboronic acid (5.0 g, 24 mmol), sodium carbonate (6.0 g, 56 mmol) and palladium tetrakis(triphenylphosphine) (1.2 g, 1.04 mmol) in 1,4-dioxane (100 mL) and H2O (5 mL) was stirred at 90° C. under N2 for 16 h. Solid was filtered off and washed with ethyl acetate. The filtrate was concentrated under vacuum to give a residue, which was partitioned between ethyl acetate and water. The aqueous layer was separated and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate and evaporated to give a crude. It was triturated by DCM to afford 1-(2-chloro-phenyl)-5-[5-(3-methanesulfonyl-phenyl)-thiophen-2-yl]-1H-pyrazole-3-carboxylic acid methyl ester (4.8 g). The mother liquors from trituration were combined and concentrated to give a solid, which was purified by flash chromatography on silica gel eluted with EtOAc-hexane (0-60%) to afford another 2.8 g of product. The total yield was 7.6 g (80%). 1H-NMR (CDCl3): δ 8.04 (m, 1H), 7.84 (m, 1H), 7.73 (m, 1H), 7.50-7.58 (m, 4H), 7.47 (m, 1H), 7.23 (d, 1H), 7.20 (s, 1H), 6.82 (d, 1H), 3.98 (s, 3H), 3.07 (s, 3H).

Workup

  1. filtrationSolid was filtered off
  2. washwashed with ethyl acetate
  3. concentrationThe filtrate was concentrated under vacuum
  4. customto give a residue, which
  5. customwas partitioned between ethyl acetate and water
  6. customThe aqueous layer was separated
  7. extractionextracted with ethyl acetate
  8. washThe combined organic layers were washed with brine
  9. dry with materialdried over sodium sulfate
  10. customevaporated
  11. customto give a crude
  12. customIt was triturated by DCM

Sources & evidence

ORD record
ord-36452b1444ff43daa1b101162f2198a2
Source dataset
uspto-grants-2014_04
Patent number
US08703805B2

Reaction notes

Loading…