Potassium Carbonate → 3-[3-(2-Fluoro-5-nitro-pyridin-3-ylmethyl)-5-isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl]-5-methyl-benzonitrile

HRID 426266Notes

Reaction equation

HRID 426266 reaction equation
[CH:1]([C:4]1[C:9](=[O:10])[NH:8][C:7](=[O:11])[NH:6][C:5]=1[C:12]([C:14]1[CH:15]=[C:16]([CH:19]=[C:20]([CH3:22])[CH:21]=1)[C:17]#[N:18])=[O:13])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].Br[CH2:30][C:31]1[C:32]([F:40])=[N:33][CH:34]=[C:35]([N+:37]([O-:39])=[O:38])[CH:36]=1.[I-].[Li+]>CN(C=O)C.C(OCC)(=O)C>[F:40][C:32]1[C:31]([CH2:30][N:6]2[C:5]([C:12]([C:14]3[CH:15]=[C:16]([CH:19]=[C:20]([CH3:22])[CH:21]=3)[C:17]#[N:18])=[O:13])=[C:4]([CH:1]([CH3:3])[CH3:2])[C:9](=[O:10])[NH:8][C:7]2=[O:11])=[CH:36][C:35]([N+:37]([O-:39])=[O:38])=[CH:34][N:33]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 66321Lithium iodideHCID 468803773-(5-Isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl)-5-methyl-benzonitrileHCID 596868623-Bromomethyl-2-fluoro-5-nitro-pyridine

Product 1

HCID 591847093-[3-(2-Fluoro-5-nitro-pyridin-3-ylmethyl)-5-isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl]-5-methyl-benzonitrileYield 34.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-(5-Isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl)-5-methyl-benzonitrile (37 mg, 0.124 mmol, 1.2 eq.) was dissolved in 1.5 mL DMF. Potassium carbonate (14 mg, 1 eq.) was added and the reaction was stirred at room temperature for 10 minutes. 3-Bromomethyl-2-fluoro-5-nitro-pyridine (27 mg, 0.103 mmol, 1 eq.) and lithium iodide (14 mg, 1 eq.) were added. The reaction was stirred at room temperature for 2 hours. Ethyl acetate was added to the reaction mixture, followed by washing with brine. The organic layer was concentrated down and purified (silica gel, 0-80% EtOAC/hexane) to give white powder (16 mg, 34%). LC-MS shows 449.9 (M−1). 1H NMR (300 MHz, CDCl3): δ 8.98 (d, 2H), 8.48 (m, 1H), 7.98 (s, 1H), 7.93 (s, 1H), 7.78 (m, 2H), 5.08 (d, 1H), 4.56 (d, 1H), 2.50 (s, 3H), 2.22 (m, 1H), 1.22 (dd, 6H).

Workup

  1. stirringThe reaction was stirred at room temperature for 2 hours
  2. washby washing with brine
  3. concentrationThe organic layer was concentrated down
  4. custompurified (silica gel, 0-80% EtOAC/hexane)

Sources & evidence

ORD record
ord-1d45665ea9884023be4ca37bbc2fdb6a
Source dataset
uspto-grants-2012_01
Patent number
US08106064B2

Reaction notes

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