Sodium Carbonate → 2-(3-Fluoro-phenyl)-pyrimidine-5-carboxylic acid 3-methylsulfamoyl-benzylamide

HRID 219677Notes

Reaction equation

HRID 219677 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[CH:12][C:11]([C:14]([OH:16])=O)=[CH:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1.C(Cl)(=O)C(Cl)=O.Cl.[NH2:24][CH2:25][C:26]1[CH:27]=[C:28]([S:32]([NH:35][CH3:36])(=[O:34])=[O:33])[CH:29]=[CH:30][CH:31]=1.C(=O)([O-])[O-].[Na+].[Na+]>O.C1(C)C=CC=CC=1.CN(C=O)C.C(Cl)Cl>[CH3:36][NH:35][S:32]([C:28]1[CH:27]=[C:26]([CH:31]=[CH:30][CH:29]=1)[CH2:25][NH:24][C:14]([C:11]1[CH:12]=[N:13][C:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=2)=[N:9][CH:10]=1)=[O:16])(=[O:33])=[O:34]

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 65578Oxalyl chlorideHCID 450733632-(3-Fluorophenyl)pyrimidine-5-carboxylic acidHCID 691225733-Methylsulfamoylbenzylamine hydrochloride

Product 1

HCID 166660252-(3-Fluoro-phenyl)-pyrimidine-5-carboxylic acid 3-methylsulfamoyl-benzylamideYield 40%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a mixture of 2-(3-fluoro-phenyl)-pyrimidine-5-carboxylic acid (545 mg, 2.5 mmol) and DCM (35 mL) is added oxalyl chloride (635 mg, 5 mmol) followed by the addition of DMF (20 μL). The reaction is stirred at room temperature for 3 hours. Anhydrous toluene (10 mL) is added and the reaction mixture is concentrated in vacuo. The residue is dissolved in EtOAc (30 mL). The resulting solution is added to a mixture of 3-aminomethyl-N-methyl-benzenesulfonamide hydrochloride (590 mg, 2.5 mmol), sodium carbonate (530 mg, 5 mmol) and water (10 mL) at 0° C. The resulting reaction mixture is warmed to room temperature and stirred overnight. Approximately 80% of EtOAc is removed in vacuo, and heptane is added to precipitate the product. The precipitate is collected by filteration, and recrystallized twice in EtOAc to afford 2-(3-fluoro-phenyl)-pyrimidine-5-carboxylic acid 3-methylsulfamoyl-benzylamide (400 mg). The mother liquors are concentrated and the residue is purified by flash chromatography to afford additional 2-(3-fluoro-phenyl)-pyrimidine-5-carboxylic acid 3-methylsulfamoyl-benzylamide (130 mg) as a powder. MS: 401 (M+H); 1H NMR (300 MHz, DMSO-d6): δ 2.41 (d, 3H), 4.64 (d, 2H), 7.42-7.50 (m, 2H), 7.57-7.70 (m, 4H), 7.78 (s, 1H), 8.16 (d, 1H), 8.31 (d, 1H), 9.33 (s, 2H), 9.53 (t, 1H). IC50=9.5 nM.

Workup

  1. concentrationthe reaction mixture is concentrated in vacuo
  2. dissolutionThe residue is dissolved in EtOAc (30 mL)
  3. customThe resulting reaction mixture
  4. temperatureis warmed to room temperature
  5. stirringstirred overnight
  6. customApproximately 80% of EtOAc is removed in vacuo, and heptane
  7. additionis added
  8. customto precipitate the product
  9. customThe precipitate is collected by filteration
  10. customrecrystallized twice in EtOAc

Sources & evidence

ORD record
ord-a6470148518247a2adb0ef377be09718
Source dataset
uspto-grants-2012_06
Patent number
US08202863B2

Reaction notes

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