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

HRID 426277Notes

Reaction equation

HRID 426277 reaction equation
[C: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])=[CH2:2].[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(OCC)(=O)C>[F:23][C:24]1[CH:29]=[C:28]([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]([C:1]([CH3:3])=[CH2:2])[C:9](=[O:10])[NH:8][C:7]2=[O:11])[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

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 66321Lithium iodideHCID 59184646Methanesulfonic acid 2-fluoro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl esterHCID 591846913-(5-Isopropenyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl)-5-methyl-benzonitrile

Product 1

HCID 591847123-{3-[2-Fluoro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl]-5-isopropenyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl}-5-methyl-benzonitrileYield 49%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 3-(5-isopropenyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl)-5-methyl-benzonitrile (0.0375 g, 0.127 mmol), methanesulfonic acid 2-fluoro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl ester (0.024 g, 0.072 mmol), lithium iodide (0.0048 g, 0.036 mmol) and potassium carbonate (0.010 g, 0.072 mmol) in DMF (1.0 mL) was stirred at 0° C. for 2 h, then warmed to rt. After 6 h, reaction mixture was diluted with ethyl acetate, washed with water (2×), dried (MgSO4), concentrated and purified by flash column chromatography (silica gel, 10 to 50% ethyl acetate/hexane) to give a yellow solid (0.019 g, 49%). 1H NMR (300 MHz, CD3CN): δ 7.87 (s, 1H), 7.74 (s, 1H), 7.65 (s, 1H), 7.19 (d, J=8.7 Hz, 2H), 6.85 (d, J=8.7 Hz, 2H), 5.89 (s, 1H), 5.84 (s, 1H), 5.66 (br s, 1H), 5.2-4.95 (br s, 1 h), 4.92 (s, 1H), 4.70 (s, 1H), 4.5-4.2 (br s, 1H), 4.20 (d, J=5.7 Hz, 2H), 3.75 (s, 3H), 2.30 (s, 3H), 1.67 (s, 3H). Mass spectrum: 538.1 (M+H)+.

Workup

  1. customreaction mixture
  2. washwashed with water (2×)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. custompurified by flash column chromatography (silica gel, 10 to 50% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-eef99701c4d546dc93f79199b57ab382
Source dataset
uspto-grants-2012_01
Patent number
US08106064B2

Reaction notes

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