Imidazole → HCID 14624251, compound

HRID 2073514Notes

Reaction equation

HRID 2073514 reaction equation
[NH:1]1[CH:5]=[CH:4][N:3]=C1.S(Cl)(Cl)=O.[CH3:10][C:11]1[S:12][C:13]([C:19]([OH:21])=O)=[C:14]([CH:16]([CH3:18])[CH3:17])[N:15]=1.[S:22]1[CH:26]=[CH:25][CH:24]=[C:23]1NCC#N>O1CCCC1>[CH3:10][C:11]1[S:12][C:13]([C:19]([NH:3][CH:4]([C:23]2[S:22][CH:26]=[CH:25][CH:24]=2)[C:5]#[N:1])=[O:21])=[C:14]([CH:16]([CH3:17])[CH3:18])[N:15]=1

Participants

6

Reactant 4

HCID 795ImidazoleHCID 24386Thionyl ChlorideHCID 146531422-Methyl-4-(1-methylethyl)-5-thiazolecarboxylic acidHCID 18381777HCID 18381777, compound

Product 1

HCID 14624251HCID 14624251, compoundYield 48.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of imidazole (2.72 g; 40 mmol) in dry tetrahydrofuran (60 ml) was added dropwise thionyl chloride (1.20 g; 10 mmol) under ice-cooling while stirring. After the resultant mixture was turned to room temperature, 2-methyl-4-isopropyl-5-thiazolecarboxylic acid (1.85 g; 10 mmol) was added thereto at once, and stirring was continued for 1 hour. To the mixture was added dropwise a solution of 2-(2-thienyl)aminoacetonitrile (1.65 g; 12 mmol) in dry tetrahydrofuran under ice-cooling, and the resultant mixture was stirred at room temperature for 3 hours. After completion of the reaction, tetrahydrofuran was removed under reduced pressure to separate the residue. Water was added to the residue, which was extracted with ethyl acetate. The ethyl acetate layer was washed with water twice, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give crude oil. The oil was purified by silica-gel column chromatography (eluent:n-hexane:ethyl acetate=2:1 volume) to give 1.49 g of 2-(2-methyl-4-isopropylthiazole-5-carboxamido)-2-(2-thienyl)acetonitrile as a viscous oil. 1H-NMR δ (CDCl3): 1.26 (6H, d, J=6 Hz), 2.62 (3H, s), 3.70 (1H, sep, J=6 Hz), 6.35 (1H, d, J=8 Hz), 6.8-7.1 (4H, m). Yield, 49%.

Workup

  1. temperaturecooling
  2. customwas turned to room temperature
  3. stirringat once, and stirring
  4. temperaturecooling
  5. customwas removed under reduced pressure
  6. customto separate the residue
  7. additionWater was added to the residue, which
  8. extractionwas extracted with ethyl acetate
  9. washThe ethyl acetate layer was washed with water twice
  10. dry with materialdried over anhydrous magnesium sulfate
  11. concentrationconcentrated under reduced pressure
  12. customto give crude oil
  13. customThe oil was purified by silica-gel column chromatography (eluent:n-hexane:ethyl acetate=2:1 volume)

Sources & evidence

ORD record
ord-e6e8cea6a8fc4f078f2cdef466797218
Source dataset
uspto-grants-1990_04
Patent number
US04918089

Reaction notes

Loading…