Diethyl chlorophosphate → 6-(2-chlorophenyl)-8-iodo-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine

HRID 1032749Notes

Reaction equation

HRID 1032749 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:14]2[CH:15]=[C:16]([I:19])[CH:17]=[CH:18][C:13]=2[NH:12][C:11](=O)[CH2:10][N:9]=1.CC(C)([O-])C.[K+].P(Cl)(OCC)(OCC)=O.[C:36]([NH:39][NH2:40])(=O)[CH3:37]>O1CCCC1.C(O)CCC>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:14]2[CH:15]=[C:16]([I:19])[CH:17]=[CH:18][C:13]=2[N:12]2[C:36]([CH3:37])=[N:39][N:40]=[C:11]2[CH2:10][N:9]=1

Participants

7

Reactant 4

HCID 13139Diethyl chlorophosphateHCID 14039AcetohydrazideHCID 136203855-(2-chlorophenyl)-1,3-dihydro-7-iodo-2H-1,4-benzodiazepin-2-oneHCID 23665647Potassium tert-butoxide

Product 1

HCID 148518946-(2-chlorophenyl)-8-iodo-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepineYield 49%

Reagents, catalysts & solvents 2

HCID 2631-ButanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 15.7 g (0.04 mol) of 5-(2-chlorophenyl)-7-iodo-1,3-dihydro-2H-1,4-benzodiazepin-2-one in 350 ml of tetrahydrofuran was cooled to -30° C. potassium t-butoxide. 4.9 g (0.044 mol) was added and stirring under nitrogen was continued for 30 minutes at -10° to -5° C. Diethyl chlorophosphate, 6.6 ml, was then added and the mixture was stirred at this temperature for another 30 minutes. Following the addition of 3.4 g of acetyl hydrazine, stirring without cooling was continued for 1 hour and 150 ml of n-butanol was added. The tetrahydrofuran was distilled out of the reaction mixture over a period of 45 minutes. The residue was partitioned between water and toluene. The organic phase was washed with brine, dried over sodium sulfate and evaporated down to a small volume. The precipitated crystals were collected to leave 14 g of crude product which was purified by chromatography over 250 g of silica gel using 5% ethanol (V/V) in methylene chloride. The clean fractions were combined and evaporated. Crystallization from tetrahydrofuran/ethanol gave 8.5 g (49%) of 6-(2-chlorophenyl)-8-iodo-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine with m.p. 290°-292° C.

Workup

  1. addition4.9 g (0.044 mol) was added
  2. stirringthe mixture was stirred at this temperature for another 30 minutes
  3. stirringstirring
  4. temperaturewithout cooling
  5. waitwas continued for 1 hour
  6. distillationThe tetrahydrofuran was distilled out of the reaction mixture over a period of 45 minutes
  7. customThe residue was partitioned between water and toluene
  8. washThe organic phase was washed with brine
  9. dry with materialdried over sodium sulfate
  10. customevaporated down to a small volume
  11. customThe precipitated crystals were collected
  12. customto leave 14 g of crude product which
  13. customwas purified by chromatography over 250 g of silica gel using 5% ethanol (V/V) in methylene chloride
  14. customevaporated
  15. customCrystallization from tetrahydrofuran/ethanol

Sources & evidence

ORD record
ord-176f1b296f5948688d13ee96071b9c93
Source dataset
uspto-grants-1990_09
Patent number
US04959361

Reaction notes

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