Sodium Bicarbonate → HCID 21265986, compound

HRID 566294Notes

Reaction equation

HRID 566294 reaction equation
Cl[CH2:2][C:3]1[N:4]=[C:5]2[CH2:11][N:10]=[C:9]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[Cl:18])[C:8]3[CH:19]=[C:20]([N+:23]([O-:25])=[O:24])[CH:21]=[CH:22][C:7]=3[N:6]2[CH:26]=1.C(=O)([O-])[OH:28].[Na+]>O1CCOCC1.O>[Cl:18][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[C:9]1[C:8]2[CH:19]=[C:20]([N+:23]([O-:25])=[O:24])[CH:21]=[CH:22][C:7]=2[N:6]2[CH:26]=[C:3]([CH2:2][OH:28])[N:4]=[C:5]2[CH2:11][N:10]=1

Participants

5

Reactant 2

HCID 516892Sodium BicarbonateHCID 21266013HCID 21266013, compound

Product 1

HCID 21265986HCID 21265986, compoundYield 54.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 2.7 g of 2-chloromethyl-6-(2-chlorophenyl)-8-nitro-4H-imidazo [1,2-a][1,4]benzodiazepine in 30 ml of dioxan was treated with a solution of 0.74 g of sodium hydrogen carbonate in 10 ml of water and the mixture was stirred at 80° C. for 2.5 h. The mixture was filtered and the filtrate was made neutral with aqueous 3N hydrochloric acid. The filtrate was evaporated in a vacuum and the residue was taken up in chloroform and water. The chloroform phase was washed with water, dried over sodium sulphate and evaporated in a vacuum. The residue was crystallized in 30 ml of ethyl acetate and diethyl ether and filtered. The crystals were dissolved in dichloromethane and chromatographed over 75 g of silica gel. With dichloromethane/ ethanol 99:1, 98:2 and 97:3 there were eluted small amounts of different impurities, with dichloromethane/ethanol 95:5 there was eluted 6-(2-chlorophenyl)-8-nitro-4H-imidazo[1,2-a][1,4]benzodiazepine-2-methanol. After recrystallization from ethyl acetate there were obtained 1.4 g of pure 6-(2-chlorophenyl)-8-nitro-4H-imidazo[1,2-a][1,4]benzodiazepine-2-methanol of m.p. 173-174° C. which was converted into the methane-sulphonate (m.p. 211-212° C.).

Workup

  1. filtrationThe mixture was filtered
  2. customThe filtrate was evaporated in a vacuum
  3. washThe chloroform phase was washed with water
  4. dry with materialdried over sodium sulphate
  5. customevaporated in a vacuum
  6. customThe residue was crystallized in 30 ml of ethyl acetate
  7. filtrationdiethyl ether and filtered
  8. dissolutionThe crystals were dissolved in dichloromethane
  9. customchromatographed over 75 g of silica gel
  10. washWith dichloromethane/ ethanol 99:1, 98:2 and 97:3 there were eluted small amounts of different impurities
  11. washwith dichloromethane/ethanol 95:5 there was eluted 6-(2-chlorophenyl)-8-nitro-4H-imidazo[1,2-a][1,4]benzodiazepine-2-methanol
  12. customAfter recrystallization from ethyl acetate

Sources & evidence

ORD record
ord-ea503447495b48879a98d8d48dd3d409
Source dataset
uspto-grants-2001_01
Patent number
US06174881B1

Reaction notes

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