Triethylamine → HCID 25214954, compound

HRID 2194758Notes

Reaction equation

HRID 2194758 reaction equation
[CH2:1](O)[CH2:2][CH:3]=[CH2:4].C(N(CC)CC)C.CS(Cl)(=O)=O.[CH:18]([C:21]1[C:26](=[O:27])[NH:25][C:24](=[O:28])[NH:23][C:22]=1[C:29]([C:31]1[CH:32]=[C:33]([CH:36]=[C:37]([CH3:39])[CH:38]=1)[C:34]#[N:35])=[O:30])([CH3:20])[CH3:19].C(=O)([O-])[O-].[K+].[K+].[I-].[Li+]>C(Cl)(Cl)Cl.ClCCl.CN(C=O)C>[CH2:4]([N:23]1[C:22]([C:29]([C:31]2[CH:32]=[C:33]([CH:36]=[C:37]([CH3:39])[CH:38]=2)[C:34]#[N:35])=[O:30])=[C:21]([CH:18]([CH3:20])[CH3:19])[C:26](=[O:27])[NH:25][C:24]1=[O:28])[CH2:3][CH:2]=[CH2:1]

Participants

10

Reactant 6

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 66321Lithium iodideHCID 693893-Buten-1-olHCID 468803773-(5-Isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl)-5-methyl-benzonitrile2×

Product 1

HCID 25214954HCID 25214954, compoundYield 30.4%

Reagents, catalysts & solvents 3

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 3-butene-1-ol (216 mg, 3 mmol) in chloroform (20 mL) cooled in an ice bath under nitrogen atmosphere, was added triethylamine (630 μL, 4.5 mmol) and methanesulfonyl chloride (270 μL, 3.6 mmol) was added dropwise. After stirring for 1.1 hr., the reaction mixture was diluted with dichloromethane and washed with sat. aqueous sodium bicarbonate, dried with anhydrous magnesium sulfate, filtered, and evaporated in vacuo. The residue was further dried in high vacuum for ca. 20 min. and mixed with 3-(5-isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl)-5-methyl-benzonitrile (Compound 1) (891 mg, 3 mmol), powdered anhydrous potassium carbonate (414 mg, 3.6 mmol), and lithium iodide (402 mg, 3 mmol). DMF (15 mL) was then added to the mixture and stirred for overnight in an oil bath (40-50° C.). After evaporation of DMF, the residue was dissolved in methanol-chloroform (1:9) and filtered through a celite pad. The filtrate was then evaporated in vacuo and the residue was purified by silica gel column chromatography (eluent, ethyl acetate:hexane (1:2)) to afford 320 mg (30%) of 3-(3-but-3-enyl-5-isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl)-5-methyl-benzonitrile (79) as a white foam. Recrystallization from ether-hexane resulted a white solid. m.p. 133-134° C.; 1H-NMR (300 MHz, CDCl3) δ 1.13 (3H, d, J=6.9 Hz), 1.22 (3H, d, J=6.9 Hz), 2.19-2.34 (3H, m), 2.54 (3H, s), 3.15 (1H, m), 3.90 (1H, m), 4.94-5.02 (2H, m), 5.58 (1H, m), 7.82 (1H, s), 7.96 (1H, s), 8.06 (1H, s), 8.99 (1H, s); m/z (EI) 351 (M+).

Workup

  1. additionwas added dropwise
  2. washwashed with sat. 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 vacuum for ca. 20 min.
  7. stirringstirred for overnight in an oil bath (40-50° C.)
  8. customAfter evaporation of DMF
  9. dissolutionthe residue was dissolved in methanol-chloroform (1:9)
  10. filtrationfiltered through a celite pad
  11. customThe filtrate was then evaporated in vacuo
  12. customthe residue was purified by silica gel column chromatography (eluent, ethyl acetate:hexane (1:2))

Sources & evidence

ORD record
ord-e15d3a159170459396baa27e9edb1a9c
Source dataset
uspto-grants-2012_12
Patent number
US08334295B2

Reaction notes

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