Sodium hydride → HCID 25099827, compound

HRID 2381984Notes

Reaction equation

HRID 2381984 reaction equation
Cl.Cl.[N:3]1([NH:9][C:10]([C:12]2[CH:13]=[N:14][C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[N:16][CH:17]=2)=[O:11])[CH2:8][CH2:7][NH:6][CH2:5][CH2:4]1.Br[CH:25]1[CH2:29][CH2:28][O:27][C:26]1=[O:30].[H-].[Na+]>CN(C=O)C>[O:30]=[C:26]1[CH:25]([N:6]2[CH2:5][CH2:4][N:3]([NH:9][C:10]([C:12]3[CH:17]=[N:16][C:15]([C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=4)=[N:14][CH:13]=3)=[O:11])[CH2:8][CH2:7]2)[CH2:29][CH2:28][O:27]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 954632(3H)-Furanone, 3-bromodihydro-HCID 68553079HCID 68553079, compound

Product 1

HCID 25099827HCID 25099827, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 2-phenyl-pyrimidine-5-carboxylic acid piperazin-1-ylamide dihydrochloride (0.45 mmol) and bromo-dihydro-furan-2-one (1.8 mmol) in DMF (10 mL) is stirred under N2 at 0° C. for 15 min, then NaH (60%, 1.8 mmol) is added and the mixture is warmed to rt and stirred overnight. The mixture is quenched with water, and extracted with EtOAC. The organic layer is dried (Na2SO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 0-2% methanol in DCM to afford give 2-phenyl-pyrimidine-5-carboxylic acid [4-(2-oxo-tetrahydro-furan-3-yl)-piperazin-1-yl]-amide (120 mg, 73%) as a solid. MS: 368 (M+H); 1H NMR (300 MHz, CDCl3): δ 2.34 (s, 2H), 2.50-3.30 (m, 8H), 3.42-3.70 (m, H), 4.17-4.50 (m, 2H), 7.34-7.68 (m, 3H), 8.50 (d, 2H), 9.06-9.38 (d, 2H). IC50=26 nM.

Workup

  1. customThe mixture is quenched with water
  2. extractionextracted with EtOAC
  3. dry with materialThe organic layer is dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue is purified by silica gel chromatography
  7. washeluting with 0-2% methanol in DCM
  8. customto afford

Sources & evidence

ORD record
ord-8bc763b614a94614a4d4a5ecbc20ea82
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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