Triethylamine → HCID 59686869, compound

HRID 426149Notes

Reaction equation

HRID 426149 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:10]=[C:9]([CH2:11]O)[CH:8]=[CH:7][N:6]=1)=[O:4].C([N:15]([CH2:18][CH3:19])CC)C.CS(Cl)(=O)=O.[CH:25]([C:28]1[C:33](=[O:34])[NH:32][C:31](=[O:35])[NH:30][C:29]=1OC1C=C(C=C(C)C=1)C#N)([CH3:27])[CH3:26].[C:46](=[O:49])([O-])[O-].[K+].[K+].[I-].[Li+]>C(Cl)(Cl)Cl.CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[CH:10]=[C:9]([CH2:11][N:30]2[C:29]([C:46](=[O:49])[C:5]3[CH:10]=[C:9]([CH3:11])[CH:8]=[C:19]([C:18]#[N:15])[CH:3]=3)=[C:28]([CH:25]([CH3:26])[CH3:27])[C:33](=[O:34])[NH:32][C:31]2=[O:35])[CH:8]=[CH:7][N:6]=1)=[O:4]

Participants

9

Reactant 6

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 66321Lithium iodideHCID 23093785Methyl 4-(hydroxymethyl)pyridine-2-carboxylateHCID 596868373-(5-Isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidin-4-yloxy)-5-methyl-benzonitrile

Product 1

HCID 59686869HCID 59686869, compoundYield 93.4%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 2-methoxycarbonylpyridine-4-methanol (222 mg, 1.3 mmol) in chloroform (10 ml) cooled in an ice bath under nitrogen atmosphere, was added triethylamine (279 μl, 2 mmol) and methanesulfonyl chloride (120 μl, 1.5 mmol) was added dropwise. After stirring for 1.1 hr., the reaction mixture was washed with saturated aqueous sodium bicarbonate, dried with anhydrous magnesium sulfate, filtered, and evaporated in vacuo. The residue was further dried in high vacuo for ca. 20 min. and mixed with (73) (394 mg, 1.3 mmol), powdered anhydrous potassium carbonate (183 mg, 1.3 mmol), and lithium iodide (178 mg, 1.3 mmol). DMF (7 ml) was then added to the mixture at room temperature and stirred for overnight. After evaporation of DMF, the residue was dissolved in methanol-chloroform (1:9) and filtered through celite pad. The filtrate was then evaporated in vacuo and the residue was purified by silica gel column chromatography (eluent, EA:hexanes (4:1)) to afford 271 mg (45%) of a white foam. 1H-NMR (200 MHz, CDCl3) δ 1.13 (3H, d, J=6.8 Hz), 1.23 (3H, d, J=6.8 Hz), 2.23 (1H, m), 2.37 (3H, s), 4.00 (3H, s), 4.66 (1H, d, J=17.0 Hz), 5.11 (1H, d, J=17.0 Hz), 7.23 (1H, m), 7.65 (2H, s), 7.73 (1H, s), 7.88 (1H, s), 8.55 (1H, d, J=5.2 Hz), 9.56 (1H, s).

Workup

  1. additionwas added dropwise
  2. wash, the reaction mixture was washed with saturated aqueous sodium bicarbonate
  3. dry with materialdried with anhydrous magnesium sulfate
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customThe residue was further dried in high vacuo for ca. 20 min.
  7. stirringstirred for overnight
  8. customAfter evaporation of DMF
  9. dissolutionthe residue was dissolved in methanol-chloroform (1:9)
  10. filtrationfiltered through celite pad
  11. customThe filtrate was then evaporated in vacuo
  12. customthe residue was purified by silica gel column chromatography (eluent, EA:hexanes (4:1))

Sources & evidence

ORD record
ord-334bd6a7f9024c8e871f9b4fce3e491d
Source dataset
uspto-grants-2012_01
Patent number
US08106064B2

Reaction notes

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