Potassium Carbonate → 3-{5-Dimethylamino-3-[2-fluoro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl]-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl}-5-methyl-benzonitrile

HRID 426271Notes

Reaction equation

HRID 426271 reaction equation
[CH3:1][N:2]([CH3:22])[C:3]1[C:8](=[O:9])[NH:7][C:6](=[O:10])[NH:5][C:4]=1[C:11]([C:13]1[CH:14]=[C:15]([CH:18]=[C:19]([CH3:21])[CH:20]=1)[C:16]#[N:17])=[O:12].[F:23][C:24]1[CH:29]=[C:28]([CH2:30]OS(C)(=O)=O)[CH:27]=[C:26]([NH:36][CH2:37][C:38]2[CH:43]=[CH:42][C:41]([O:44][CH3:45])=[CH:40][CH:39]=2)[N:25]=1.[I-].[Li+].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.C(#N)C>[CH3:1][N:2]([CH3:22])[C:3]1[C:8](=[O:9])[NH:7][C:6](=[O:10])[N:5]([CH2:30][C:28]2[CH:27]=[C:26]([NH:36][CH2:37][C:38]3[CH:43]=[CH:42][C:41]([O:44][CH3:45])=[CH:40][CH:39]=3)[N:25]=[C:24]([F:23])[CH:29]=2)[C:4]=1[C:11]([C:13]1[CH:14]=[C:15]([CH:18]=[C:19]([CH3:21])[CH:20]=1)[C:16]#[N:17])=[O:12]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 66321Lithium iodideHCID 59184646Methanesulfonic acid 2-fluoro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl esterHCID 591846513-(5-Dimethylamino-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl)-5-methyl-benzonitrile

Product 1

HCID 591848143-{5-Dimethylamino-3-[2-fluoro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl]-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl}-5-methyl-benzonitrile

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

A solution 3-(5-dimethylamino-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl)-5-methyl-benzonitrile (0.0087 g, 0.0292 mmol), methanesulfonic acid 2-fluoro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl ester (0.0095 g, 0.0292 mmol), lithium iodide (0.002 g, 0.0146 mmol) and potassium carbonate (0.004 g, 0.0292 mmol) in DMF (3.0 mL) was stirred at 0° C. for 7 h. Reaction mixture was diluted with acetonitrile and purified by reverse phase HPLC (Phenomenex Synergi® column, 5 to 100% acetonitrile/H2O) to give an yellow powder after lyophilization (0.0063 g, 40%). 1H NMR (300 MHz, CDCl3): δ 8.55 (br s, 1H), 7.62 (s, 1H), 7.52 (s, 1H), 7.49 (s, 1H), 7.22 (s, 1H), 7.19 (d, J=8.4 Hz, 2H), 6.85 (d, J=8.4 Hz, 2H), 5.77 (d, J=8.4 Hz, 1H), 4.22 (s, 2H), 3.77 (s, 3H), 2.39 (s, 6H). Mass spectrum: 543.1 (M+H)+.

Workup

  1. customReaction mixture
  2. custompurified by reverse phase HPLC (Phenomenex Synergi® column, 5 to 100% acetonitrile/H2O)
  3. customto give an yellow powder after lyophilization (0.0063 g, 40%)

Sources & evidence

ORD record
ord-389cb3f8c5004c37b5f9250826009ade
Source dataset
uspto-grants-2012_01
Patent number
US08106064B2

Reaction notes

Loading…