Triethylamine → 3-(3-{3-[2-Fluoro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl]-5-isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl}-phenyl)-acrylonitrile

HRID 426209Notes

Reaction equation

HRID 426209 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([CH2:8]O)[CH:5]=[C:4]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=2)[N:3]=1.C(N(CC)CC)C.CS(Cl)(=O)=O.[CH:32]([C:35]1[C:40](=[O:41])[NH:39][C:38](=[O:42])[NH:37][C:36]=1[C:43]([C:45]1[CH:46]=[C:47]([CH:51]=[CH:52][C:53]#[N:54])[CH:48]=[CH:49][CH:50]=1)=[O:44])([CH3:34])[CH3:33].C(=O)([O-])[O-].[K+].[K+].[I-].[Li+]>C(Cl)(Cl)Cl.ClCCl.CN(C=O)C>[F:1][C:2]1[CH:7]=[C:6]([CH2:8][N:37]2[C:36]([C:43]([C:45]3[CH:46]=[C:47]([CH:51]=[CH:52][C:53]#[N:54])[CH:48]=[CH:49][CH:50]=3)=[O:44])=[C:35]([CH:32]([CH3:33])[CH3:34])[C:40](=[O:41])[NH:39][C:38]2=[O:42])[CH:5]=[C:4]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=2)[N:3]=1

Participants

10

Reactant 6

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 66321Lithium iodideHCID 59184650HCID 59184650, compoundHCID 667054933-[3-(5-Isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl)-phenyl]-acrylonitrile

Product 1

HCID 667054883-(3-{3-[2-Fluoro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl]-5-isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl}-phenyl)-acrylonitrileYield 46.2%

Reagents, catalysts & solvents 3

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 2-fluoro-6-(p-methoxybenzylamino)-4-pyridine-methanol (186 mg, 0.712 mmol) in chloroform (7 ml) at 0° C. (ice bath), was added triethylamine (150 μl, 1.07 mmol) followed by methanesulfonyl chloride (64 μl, 0.85 mmol). After stirring for 1.5 hr., the mixture was diluted with dichloromethane, washed with aqueous saturated sodium bicarbonate solution, dried with anhydrous magnesium sulfate, filtered, and evaporated in vacuo. The residue was further dried in high vacuo and mixed with 3-[3-(5-isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl)-phenyl]-acrylonitrile (309 mg, 0.712 mmol), anhydrous powdered potassium carbonate (110 mg, 0.8 mmol), lithium iodide (107 mg, 0.8 mmol). Anhydrous DMF (5 ml) was then added into the mixture and stirred for overnight at room temperature. The mixture was evaporated in vacuo. The residue was dissolved in methanol-dichloromethane (1:9), filtered through celite pad, and evaporated in vacuo to give a pale yellow foam. The crude product was purified by silica gel column chromatography (eluent, EA:hexanes (1:2); The fraction of Rf=0.14 was collected.) to afford 182 mg (46%) of a pale yellow syrup.

Workup

  1. washwashed with aqueous saturated sodium bicarbonate solution
  2. dry with materialdried with anhydrous magnesium sulfate
  3. filtrationfiltered
  4. customevaporated in vacuo
  5. customThe residue was further dried in high vacuo
  6. stirringstirred for overnight at room temperature
  7. customThe mixture was evaporated in vacuo
  8. dissolutionThe residue was dissolved in methanol-dichloromethane (1:9)
  9. filtrationfiltered through celite pad
  10. customevaporated in vacuo
  11. customto give a pale yellow foam
  12. customThe crude product was purified by silica gel column chromatography (eluent, EA:hexanes (1:2)
  13. customThe fraction of Rf=0.14 was collected

Sources & evidence

ORD record
ord-202ec8a3951d401fba624f68e125cc4f
Source dataset
uspto-grants-2012_01
Patent number
US08106064B2

Reaction notes

Loading…