Iodoethane → 6-(4-chlorophenyl)-4-ethyl-1-methyl-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepin-5(6H)-one

HRID 1485425Notes

Reaction equation

HRID 1485425 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:14](=[O:15])[CH2:13][C:12]3=[N:16][N:17]=[C:18]([CH3:19])[N:11]3[C:10]3[CH:20]=[CH:21][CH:22]=[CH:23][C:9]2=3)=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].I[CH2:35][CH3:36]>O1CCCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:14](=[O:15])[CH:13]([CH2:35][CH3:36])[C:12]3=[N:16][N:17]=[C:18]([CH3:19])[N:11]3[C:10]3[CH:20]=[CH:21][CH:22]=[CH:23][C:9]2=3)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 6340IodoethaneHCID 2733832Lithium HexamethyldisilazideHCID 709795286-(4-chlorophenyl)-1-methyl-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepin-5(6H)-one

Product 1

HCID 709792176-(4-chlorophenyl)-4-ethyl-1-methyl-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepin-5(6H)-oneYield 18.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Into a 50 mL flask evacuated and brimmed with dry nitrogen, was charged with a solution of 6-(4-chlorophenyl)-1-methyl-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepin-5(6H)-one (Example 1, step 5; 100 mg, 0.31 mmol) in anhydrous tetrahydrofuran (10 mL). To this mixture, was added lithium bis(trimethylsilyl)amide (tetrahydrofuran solution) (0.17 mL, 0.33 mmol) at −78° C. The mixture was stirred at the same temperature for 1 hour, and then warmed to room temperature, maintained at the same temperature for 2 hours. Iodoethane (92.04 mg, 0.59 mmol) was added. The mixture was stirred at room temperature for another 2 hours. The reaction was quenched by ammonium chloride aqueous (5 mL), extracted with ethyl acetate (5 mL*3). The crude product was purified by column chromatography (silica gel, dichloromethane/methanol=25:1) to give 6-(4-chlorophenyl)-4-ethyl-1-methyl-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepin-5(6H)-one as a light yellow solid (20.0 mg, 18%). LRMS (M+H)+: calcd 352.11. found 352.

Workup

  1. customInto a 50 mL flask evacuated
  2. temperaturemaintained at the same temperature for 2 hours
  3. stirringThe mixture was stirred at room temperature for another 2 hours
  4. customThe reaction was quenched by ammonium chloride aqueous (5 mL)
  5. extractionextracted with ethyl acetate (5 mL*3)
  6. customThe crude product was purified by column chromatography (silica gel, dichloromethane/methanol=25:1)

Sources & evidence

ORD record
ord-653e8c64f8b3440fa03e8ba677d715ea
Source dataset
uspto-grants-2016_08
Patent number
US09422292B2

Reaction notes

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