Tetrahydrofuran → HCID 10098027, compound

HRID 1742112Notes

Reaction equation

HRID 1742112 reaction equation
[NH2:1][C:2]1[CH:26]=[CH:25][C:5]([CH2:6][N:7]2[C:11]([S:12][CH2:13][C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)=[N:10][N:9]=[C:8]2[CH2:21][CH2:22][CH2:23][CH3:24])=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.[C:36]([C:38]1[CH:45]=[CH:44][CH:43]=[CH:42][C:39]=1[CH2:40]Cl)#[N:37].C1C[O:49]CC1>CCCCCC>[CH2:21]([C:8]1[N:7]([CH2:6][C:5]2[CH:4]=[CH:3][C:2]([NH:1][C:40](=[O:49])[C:39]3[CH:42]=[CH:43][CH:44]=[CH:45][C:38]=3[C:36]#[N:37])=[CH:26][CH:25]=2)[C:11]([S:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=2)=[N:10][N:9]=1)[CH2:22][CH2:23][CH3:24]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 69152Benzonitrile, 2-(chloromethyl)- (9CI)HCID 81531DiisopropylethylamineHCID 10385516HCID 10385516, compound

Product 1

HCID 10098027HCID 10098027, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Procedure

A solution of 450 mg (1.16 mmole) of 4-(4- aminobenzyl)-3-n-butyl-5-(4-chlorobenzylthio)-4H-1,2,4-triazole (Step B), 438 μl (325 mg, 2.52 mmole) of N,N-diisopropylethylamine and 418 mg (2.53 mmole) of 2-cyanobenzyl chloride [R. Scholl and W. Neuberger, Monatsh. Chem. 33, 507 (1911)] in 10 ml of dry THF was stirred overnight at room temperature under N2. The mixture was filtered, and the filtrate was concentrated in vacuo. The residue was dissolved in 50 ml of ethyl acetate and washed with 2×60 ml of saturated NaHCO3 solution followed by 50 ml of saturated NACl. The organic phase was then dried (MgSO4), filtered, and concentrated. A solution of the residue in CH2Cl2 was treated with approximately 2 g of silica gel, and the mixture was evaporated to give a dry powder, which was added as a slurry in hexane to the top of a silica gel column packed in the same solvent. The column was eluted briefly with hexane and then with a stepwise gradient from 1:1 hexane-EtOAc to 100% EtOAc. Two major products were eluted, the second of which correspond to the desired product. Fractions containing this material were combined and concentrated to give 229 mg (36%) of the title compound as a solid, mp 75°-77° C. dec., homogeneous by TLC in 1:3 hexane-EtOAc; mass spectrum (FAB) m/e 516 (M+1)+.

Workup

  1. filtrationThe mixture was filtered
  2. concentrationthe filtrate was concentrated in vacuo
  3. dissolutionThe residue was dissolved in 50 ml of ethyl acetate
  4. washwashed with 2×60 ml of saturated NaHCO3 solution
  5. dry with materialThe organic phase was then dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. additionA solution of the residue in CH2Cl2 was treated with approximately 2 g of silica gel
  9. customthe mixture was evaporated
  10. customto give a dry powder, which
  11. washThe column was eluted briefly with hexane
  12. washTwo major products were eluted
  13. additionFractions containing this material
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-0070c065eb824634b2f91734be8cc007
Source dataset
uspto-grants-1994_08
Patent number
US05336778

Reaction notes

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