Sodium hydride → HCID 25099272, compound

HRID 2381986Notes

Reaction equation

HRID 2381986 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.[H-].[Na+].Cl[CH2:27][C:28]([N:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1)=[O:29]>CN(C=O)C>[N:30]1([C:28](=[O:29])[CH2:27][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)[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 74040Morpholine, 4-(chloroacetyl)-HCID 68553079HCID 68553079, compound

Product 1

HCID 25099272HCID 25099272, compoundYield 14%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 2-phenyl-pyrimidine-5-carboxylic acid piperazin-1-ylamide dihydrochloride (0.43 mmol) and NaH (60%, 2.15 mmol) in DMF (10 mL) is stirred under N2 at rt for 20 min. 2-Chloro-1-morpholin-4-yl-ethanone (0.65 mmol)) is added and the reaction mixture is stirred at rt overnight. The reaction mixture is quenched with water, and extracted with EtOAc. The organic layer is separated, dried (Na2SO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 0-4% methanol in DCM to afford 2-phenyl-pyrimidine-5-carboxylic acid [4-(2-morpholin-4-yl-2-oxo-ethyl)-piperazin-1-yl]-amide (24 mg, 14%) as a solid. MS: 411 (M+H); 1H NMR (300 MHz, CDCl3): δ 2.85-3.10 (m, 2H), 3.60-4.00 (m, 12H), 4.46 (d, 2H), 4.84 (s, 2H), 7.44-7.62 (m, 3H), 8.34-8.58 (m, 2H), 9.20-9.38 (d, 2H). IC50=831.5 nM.

Workup

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

Sources & evidence

ORD record
ord-a7ab65a0d8234dab9fcee9de915047b0
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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