1,1-Dichloroacetone → HCID 21265968, compound

HRID 566304Notes

Reaction equation

HRID 566304 reaction equation
[NH2:1][C:2]1[CH2:8][N:7]=[C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=2)[C:5]2[CH:15]=[C:16]([Cl:19])[CH:17]=[CH:18][C:4]=2[N:3]=1.[Cl:20][CH2:21][C:22]([CH2:24]Cl)=O.C(=O)([O-])O.[Na+].ClC(Cl)C(=O)C>O1CCOCC1>[Cl:20][CH2:21][C:22]1[N:1]=[C:2]2[CH2:8][N:7]=[C:6]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=3)[C:5]3[CH:15]=[C:16]([Cl:19])[CH:17]=[CH:18][C:4]=3[N:3]2[CH:24]=1

Participants

6

Reactant 4

HCID 105671,1-DichloroacetoneHCID 107931,3-DichloroacetoneHCID 516892Sodium Bicarbonate2×HCID 212660152-amino-7-chloro-5-(2-pyridyl)-3H-1,4-benzodiazepine

Product 1

HCID 21265968HCID 21265968, compoundYield 43.6%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of 16.3 g of 2-amino-7-chloro-5-(2-pyridyl)-3H-1,4-benzodiazepine and 8.4 g of 1,3-dichloroacetone in 600 ml of dioxan was treated with 5.6 g of anhydrous sodium hydrogen carbonate and stirred at 100°0 C. for 16 h. A further 0.84 g of dichloroacetone and 0.56 g of anhydrous sodium hydrogen carbonate were added and the mixture was stirred at 100° C. for a further 8 h. The mixture was evaporated in a vacuum and the residue was partitioned between chloroform and water. The aqueous phase was extracted twice with dichloromethane. The combined organic phases were evaporated in a vacuum. The residue was dissolved in dichloromethane and chromatographed over 800 g of silica gel. With dichloromethane/ethanol 197:3 there were eluted small amounts of impurities, with dichloromethane/ethanol 196:4 there were eluted 10.2 g of the desired product. After recrystallization from ethyl acetate there were obtained 9.0 g of 2-chloromethyl-8-chloro-6-(2-pyridyl)-4H-imidazo[1,2-a][1,4]benzodiazepine of m.p. 161° C.

Workup

  1. stirringthe mixture was stirred at 100° C. for a further 8 h
  2. customThe mixture was evaporated in a vacuum
  3. customthe residue was partitioned between chloroform and water
  4. extractionThe aqueous phase was extracted twice with dichloromethane
  5. customThe combined organic phases were evaporated in a vacuum
  6. dissolutionThe residue was dissolved in dichloromethane
  7. customchromatographed over 800 g of silica gel
  8. washWith dichloromethane/ethanol 197:3 there were eluted small amounts of impurities
  9. washwith dichloromethane/ethanol 196:4 there were eluted 10.2 g of the desired product
  10. customAfter recrystallization from ethyl acetate

Sources & evidence

ORD record
ord-16d9dc9ada1d417f9310032a1814199d
Source dataset
uspto-grants-2001_01
Patent number
US06174881B1

Reaction notes

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