Methyl iodide → 6-(4-chlorophenyl)-1,4-dimethyl-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepin-5(6H)-one

HRID 1485376Notes

Reaction equation

HRID 1485376 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.[Li+].[CH3:25][Si]([N-][Si](C)(C)C)(C)C.CI.[NH4+].[Cl-]>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:14](=[O:15])[CH:13]([CH3:25])[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

6

Reactant 4

HCID 6328Methyl iodideHCID 25517Ammonium ChlorideHCID 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 709790516-(4-chlorophenyl)-1,4-dimethyl-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepin-5(6H)-oneYield 38.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6-(4-chlorophenyl)-1-methyl-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepin-5(6H)-one (100 mg, 0.31 mmol) in THF was added LiHMDS (0.17 mL, 0.33 mmol) at −78° C. The mixture was stirred at the same temperature for 1 h, and then CH3I (84.00 mg, 0.59 mmol) was added. The mixture was stirred at −78° C. for 2 h, then warmed to room temperature, and maintained at room temperature for 2 h. NH4Cl aqueous (15 mL) was added, and then extracted with DCM (10 mL*3). The product was purified by column chromatography (silica-gel, DCM:MEOH=30:1) to give 6-(4-chlorophenyl)-1,4-dimethyl-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepin-5(6H)-one (40.0 mg, 38%). LRMS (M+H+) m/z: calcd 338.09. found 338.

Workup

  1. stirringThe mixture was stirred at −78° C. for 2 h
  2. temperaturemaintained at room temperature for 2 h
  3. extractionextracted with DCM (10 mL*3)
  4. customThe product was purified by column chromatography (silica-gel, DCM:MEOH=30:1)

Sources & evidence

ORD record
ord-45c5b58186d641ab91987b37b3daba1c
Source dataset
uspto-grants-2016_08
Patent number
US09422292B2

Reaction notes

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