1,1-Dichloroacetone → HCID 21266016, compound

HRID 566309Notes

Reaction equation

HRID 566309 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]([I: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]([I: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 21266001HCID 21266001, compound

Product 1

HCID 21266016HCID 21266016, compoundYield 43.8%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A, solution of 2.3 g of 2-amino-7-iodo-5-(2-pyridyl)-3H-1,4-benzodiazepine and 0.87 g of 1,3-dichloroacetone in 65 ml of dioxan was treated with 0.6 g of anhydrous sodium hydrogen carbonate and the mixture was stirred at 100° C. for 24 h. A further 0.09 g of dichloroacetone and 0.06 g of anhydrous sodium hydrogen carbonate were added and the mixture was stirred at 100° C. for a further 5 h. The mixture was evaporated in a vacuum and the residue was partitioned between chloroform and saturated aqueous sodium hydrogen carbonate solution. The aqueous phase was extracted three times with chloroform. The chloroform extracts were dried over sodium sulphate and chromatographed over 200 g of silica gel. With dichloromethane/ethanol 197:3 there were eluted small amounts of impurities, with dichloromethane/ethanol 195:5 there were eluted 1.3 g of the desired product. After recrystallization from ethyl acetate there were obtained 1.21 g of 2-chloromethyl-8-iodo-6-(2-pyridyl)-4H-imidazo [1,2-a][1,4]benzodiazepine of m.p. 216° C. (dec.).

Workup

  1. stirringthe mixture was stirred at 100° C. for a further 5 h
  2. customThe mixture was evaporated in a vacuum
  3. customthe residue was partitioned between chloroform and saturated aqueous sodium hydrogen carbonate solution
  4. extractionThe aqueous phase was extracted three times with chloroform
  5. dry with materialThe chloroform extracts were dried over sodium sulphate
  6. customchromatographed over 200 g of silica gel
  7. washWith dichloromethane/ethanol 197:3 there were eluted small amounts of impurities
  8. washwith dichloromethane/ethanol 195:5 there were eluted 1.3 g of the desired product
  9. customAfter recrystallization from ethyl acetate

Sources & evidence

ORD record
ord-82c1e6fa0cb444989951f714a7a220da
Source dataset
uspto-grants-2001_01
Patent number
US06174881B1

Reaction notes

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