Dimethylformamide → HCID 88532486, compound

HRID 1529833Notes

Reaction equation

HRID 1529833 reaction equation
[Se-2:1].[Na+].[Na+].CSC([S:12][CH3:13])=C(C#N)C#N.CCC([N:18]1C(=O)[NH:23][C:22]([CH3:26])=[C:21](Br)[C:19]1=O)C.ClCC(O[CH2:33][CH3:34])=O.[CH3:35][O-].[Na+].CN([CH:41]=[O:42])C>CO.O>[NH2:23][C:22]1[C:21]([C:19]#[N:18])=[C:33]([CH3:34])[Se:1][C:26]=1[C:13]([O:42][CH2:41][CH3:35])=[S:12]

Participants

9

Reactant 6

HCID 6228Dimethylformamide2×HCID 7751Ethyl chloroacetateHCID 9411BromacilHCID 73973Sodium selenideHCID 992292-(Bis(methylsulfanyl)methylidene)propanedinitrileHCID 10942334Sodium Methoxide

Product 1

HCID 88532486HCID 88532486, compoundYield 21%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
75 °C

Procedure

To a suspension of sodium selenide (4.6 g, 37.5 mmol) in DMF (37 mL) was added a solution of 2-[bis(methylsulfanyl)methylene]malononitrile (6.37 g, 37.5 mmol; Baraldi, P. G.; Fruttarolo, F.; Tabrizi, M. A.; Preti, D.; Romagnoli, R.; El-Kashef, H.; Moorman, A.; Varani, K.; Gessi, S.; Merighi, S.; Borea, P. A. J. Med. Chem., 2003, 46, 1229-1241; Thomae, D.; Perspicace, E.; Henryon, D.; Xu, Z.; Schneider, S.; Hesse, S.; Kirsch, G.; Seck, P. Tetrahedron, 2009, 65, 10453-10458) in DMF (18 mL) at rt for 5 min and stirred the mixture at 70-80° C. for 2 h. Then ethyl chloroacetate (6.38 mL, 75 mmol) was added dropwise to the reaction mixture and again stirred at 70-80° C. for 2 h. Then, a suspension of sodium methoxide (2.0 g, 37.5 mmol) in methanol (37 mL) was added and stirring was continued for 1.5 h at the same temperature. The mixture was allowed to rt and poured into cold water and stirred for 15 min. The solution was extracted with chloroform (3×100 mL). The combined organic layer was washed with water, brine and dried over sodium sulfate. The solution was filtered and evaporated the solvent. The residue was chromatographed over silica gel column using hexane-ethyl acetate (90:10) as eluents to give the product as a brown color solid (2.2 g, 21%), mp 128-130° C. 1H NMR (400 MHz, CDCl3): δ 5.86 (2H, br s), 4.27 (2H, q, J=7.06 Hz), 2.67 (3H, s), 1.32 (3H, t, J=7.0 Hz); LC-MS (positive ion mode): m/z 289, 291 (M+H)+.

Workup

  1. stirringagain stirred at 70-80° C. for 2 h
  2. additionwas added
  3. stirringstirring
  4. waitwas continued for 1.5 h at the same temperature
  5. customwas allowed to rt
  6. stirringstirred for 15 min
  7. extractionThe solution was extracted with chloroform (3×100 mL)
  8. washThe combined organic layer was washed with water, brine
  9. dry with materialdried over sodium sulfate
  10. filtrationThe solution was filtered
  11. customevaporated the solvent
  12. customThe residue was chromatographed over silica gel column

Sources & evidence

ORD record
ord-efd492d7ee9f405b917ec57d94506ba1
Source dataset
uspto-grants-2015_07
Patent number
US09090633B2

Reaction notes

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