Sodium hydride → 2-[(5-bromo-2-chloro-6-oxo-1(6H)-pyrimidinyl)methyl]Benzonitrile

HRID 2105310Notes

Reaction equation

[Br:1][C:2]1[C:3](=[O:9])[NH:4][C:5]([Cl:8])=[N:6][CH:7]=1.[H-].[Na+].[Br-].[Li+].Br[CH2:15][C:16]1[C:17]([C:22]#[N:23])=[CH:18][CH:19]=[CH:20][CH:21]=1>COCCOC.CCOC(C)=O.CN(C=O)C>[Br:1][C:2]1[C:3](=[O:9])[N:4]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[C:22]#[N:23])[C:5]([Cl:8])=[N:6][CH:7]=1

Participants

Conditions

Temperature: 65 °C

Procedure

5-Bromo-2-chloro-3H-pyrimidin-4-one (1.88 g, 9.0 mmol) was stirred in DME (25 mL)/DMF (5 mL) under nitrogen at 0° C. Sodium hydride (95%, 238 mg, 9.4 mmol) was added in portions. After 10 min, lithium bromide (1.56 g, 17.9 mmol) was added and the reaction stirred for 15 min at r.t. α-Bromo-o-tolunitrile (3.5 g, 17.9 mmol) was added, and the reaction stirred at 65° C. for 8 h. The solution was diluted with EtOAc, washed with brine, dried (MgSO4) and concentrated in vacuo. Purification by silica gel chromatography (1:1:1 EtOAc/hexanes/CHCl3) gave 997 mg (34%) of 2-(5-bromo-2-chloro-6-oxo-6H-pyrimidin-1-ylmethyl)-benzonitrile as a white solid. 1H NMR (400 MHz, CDCl3): δ 8.11 (s, 1H), 7.73 (dd, 1H, J=7.6, 1.2 Hz), 7.58 (dt, 1H, J=7.6, 1.2 Hz), 7.45 (t, 1H, J=7.6 Hz), 7.16 (d, 1H, J=7.6 Hz), 5.69 (s, 2H). MS (ES) [m+H] calc'd for C12H7N3OBrCl, 324, 326, 328; found 324, 326, 328.

Workup

additionwas added
washwashed with brine
dry with materialdried (MgSO4)
concentrationconcentrated in vacuo
customPurification by silica gel chromatography (1:1:1 EtOAc/hexanes/CHCl3)

Sources & evidence

ORD record: ord-f4de892624c34be398b00cac57d65800
Source dataset: uspto-grants-2009_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07579357B2

Reaction notes

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