Dimethyl Sulfoxide → 8-Chloro-1-(4-oxo-cyclohexyl)-4H,6H-2,3,5,10b-tetraaza-benzo[e]azulene-5-carboxylic acid tert-butyl ester

HRID 1966000Notes

Reaction equation

HRID 1966000 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[C:11]([O:15][C:16]([N:18]1[CH2:27][C:26]2[N:22]([C:23]([C@H:28]3[CH2:33][CH2:32][C@H:31]([OH:34])[CH2:30][CH2:29]3)=[N:24][N:25]=2)[C:21]2[CH:35]=[CH:36][C:37]([Cl:39])=[CH:38][C:20]=2[CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].C(N(CC)CC)C>ClCCl>[C:11]([O:15][C:16]([N:18]1[CH2:27][C:26]2[N:22]([C:23]([CH:28]3[CH2:29][CH2:30][C:31](=[O:34])[CH2:32][CH2:33]3)=[N:24][N:25]=2)[C:21]2[CH:35]=[CH:36][C:37]([Cl:39])=[CH:38][C:20]=2[CH2:19]1)=[O:17])([CH3:14])([CH3:12])[CH3:13]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 178451485HCID 178451485, compound

Product 1

HCID 584587428-Chloro-1-(4-oxo-cyclohexyl)-4H,6H-2,3,5,10b-tetraaza-benzo[e]azulene-5-carboxylic acid tert-butyl esterYield 90%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-50 °C

Procedure

To a solution of oxalyl chloride (0.11 ml, 1.3 mmol) in dichloromethane (8 ml) was added dimethylsulfoxide (0.21 ml, 2.6 mmol) at −60° C. The mixture was stirred for 5 minutes at −50° C. A solution of cis/trans-8-chloro-1-(4-hydroxy-cyclohexyl)-4H,6H-2,3,5,10b-tetraaza-benzo[e]azulene-5-carboxylic acid tert-butyl ester (0.046 g, 1.1 mmol) in dichloromethane (3 ml) was added at −65° C. Stirring for 30 minutes was followed by addition of triethylamine (0.77 ml, 5.5 mmol). The cooling bath was removed after 5 minutes, and the reaction mixture was stirred for 1 h. The reaction mixture was washed with one portion of aqueous saturated ammonium chloride solution. The aqueous layer was extracted with three portions of tert-butyl methyl ether. The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo. Flash-chromatography with n-heptane/ethyl acetate as eluent gave the title compound (0.41 g, 90%) as white solid. MS m/e: 417 (M+H+)

Workup

  1. stirringStirring for 30 minutes
  2. customThe cooling bath was removed after 5 minutes
  3. stirringthe reaction mixture was stirred for 1 h
  4. washThe reaction mixture was washed with one portion of aqueous saturated ammonium chloride solution
  5. extractionThe aqueous layer was extracted with three portions of tert-butyl methyl ether
  6. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b37fad99a9764cba917a8e1fc7bf5c3f
Source dataset
uspto-grants-2013_04
Patent number
US08420633B2

Reaction notes

Loading…