Sodium hydride → 1-Benzyl-3-(3-bromo-5-methyl-pyridin-2-ylamino)-5-chloro-1H-pyrazin-2-one

HRID 2060906Notes

Reaction equation

[NH2:1][C:2]1[C:7]([Br:8])=[CH:6][C:5]([CH3:9])=[CH:4][N:3]=1.[H-].[Na+].[CH2:12]([N:19]1[CH:24]=[C:23]([Cl:25])[N:22]=[C:21](Cl)[C:20]1=[O:27])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>C1COCC1>[CH2:12]([N:19]1[CH:24]=[C:23]([Cl:25])[N:22]=[C:21]([NH:1][C:2]2[C:7]([Br:8])=[CH:6][C:5]([CH3:9])=[CH:4][N:3]=2)[C:20]1=[O:27])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

Conditions

Temperature: 72 °C

Procedure

2-Amino-3-bromo-5-methyl-pyridine (1.0 g, 5.35 mmol) was added to a solution of sodium hydride (60%, 321 mg, 8.0 mmol) in dry THF (20 mL) at r.t. under nitrogen. After 30 minutes, 1-benzyl-3,5-dichloro-2(1H)-pyrazinone (see Vekemans, et. al., J. Heterocyclic Chem., 20, (1983), 919-923) (1.36 g, 5.35 mmol) was added, and the reaction stirred at 72° C. for 4 h. The solution was concentrated in vacuo and the residue was dissolved in CH2Cl2. Organics were washed with H2O and brine, dried (MgSO4), and concentrated. Purification by silica gel chromatography (2:1:1 hexanes/EtOAc/CH2Cl2) provided the title compound as a pale yellow solid (860 mg, 40%). 1H NMR (400 MHz, DMSO-d6): δ 9.51 (s, 1H), 8.27 (s, 1H), 8.00 (s, 1H), 7.43 (s, 1H), 7.29-7.39 (m, 5H), 5.07 (s, 2H), 2.29 (s, 3H). MS (ES) [m+H] calc'd for C17H14BrClN4O, 405, 407; found 405, 407.

Workup

concentrationThe solution was concentrated in vacuo
dissolutionthe residue was dissolved in CH2Cl2
washOrganics were washed with H2O and brine
dry with materialdried (MgSO4)
concentrationconcentrated
customPurification by silica gel chromatography (2:1:1 hexanes/EtOAc/CH2Cl2)

Sources & evidence

ORD record: ord-8469b8d9140d4296a811352627b2a3ab
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08278450B2

Reaction notes

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