Cyclohexanemethanol → 2,6-dichloro-4-(4,5-dihydro-3,5-dioxo-1,2,4-triazin-2(3H)-yl)-alpha,alpha-dimethylbenzeneacetonitrile

HRID 1072486Notes

Reaction equation

HRID 1072486 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([N:8]2[C:13](=[O:14])[NH:12][C:11](=[O:15])[CH:10]=[N:9]2)[CH:5]=[C:4]([Cl:16])[C:3]=1[C:17]([C:20]1SC(CC(O)=O)=C(C2C=CC=CC=2)[N:24]=1)([CH3:19])[CH3:18].C(N1C=CN=C1)(N1C=CN=C1)=O.C1(CO)CCCCC1>ClCCl>[Cl:1][C:2]1[CH:7]=[C:6]([N:8]2[C:13](=[O:14])[NH:12][C:11](=[O:15])[CH:10]=[N:9]2)[CH:5]=[C:4]([Cl:16])[C:3]=1[C:17]([CH3:19])([CH3:18])[C:20]#[N:24]

Participants

5

Reactant 3

HCID 7507CyclohexanemethanolHCID 682631,1'-CarbonyldiimidazoleHCID 158708342-[1-[2,6-dichloro-4-(4,5-dihydro-3,5-dioxo-1,2,4-triazin-2(3H)yl)phenyl]-1-methylethyl]-4-phenyl-5-thiazoleacetic acid

Product 1

HCID 114841762,6-dichloro-4-(4,5-dihydro-3,5-dioxo-1,2,4-triazin-2(3H)-yl)-alpha,alpha-dimethylbenzeneacetonitrileYield 113.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of intermediate (10) (0.00387 mole) and 1,1′-carbonylbis-1H-imidazole (0.0058 mole) in dichloromethane (40 ml) was stirred at RT for 90 minutes, then cyclohexylmethanol (0.0058 mole) was added. The mixture was stirred at RT overnight, diluted with CH2Cl2 and washed twice with an aqueous solution of NaCl. The organic layer was separated, dried (MgSO4), filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/EtOAc 50/50). The pure fractions were collected and the solvent was evaporated. The residue was crystallized from EtOAc. The precipitate was filtered off, washed with DIPE and dried at 50° C. overnight, yielding 1.43 g of compound 7 with a molecular weight of 613.5, a melting point of 180° C. and represented by the formula wherein R14 is cyclohexylmethyl.

Workup

  1. stirringThe mixture was stirred at RT overnight
  2. washwashed twice with an aqueous solution of NaCl
  3. customThe organic layer was separated
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customthe solvent was evaporated
  7. customThe residue was purified by column chromatography over silica gel (eluent: CH2Cl2/EtOAc 50/50)
  8. customThe pure fractions were collected
  9. customthe solvent was evaporated
  10. customThe residue was crystallized from EtOAc
  11. filtrationThe precipitate was filtered off
  12. washwashed with DIPE
  13. customdried at 50° C. overnight

Sources & evidence

ORD record
ord-07ebc7af780948b7a972b241fb468a0f
Source dataset
uspto-grants-2005_06
Patent number
US06911444B2

Reaction notes

Loading…