Ammonium Chloride → tert-butyl 2-(6-(4-chlorophenyl)-1-methyl-5-oxo-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepin-4-yl)acetate

HRID 1485401Notes

Reaction equation

HRID 1485401 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+].C[Si]([N-][Si](C)(C)C)(C)C.Br[CH2:35][C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37].[NH4+].[Cl-]>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:14](=[O:15])[CH:13]([CH2:35][C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[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 25517Ammonium ChlorideHCID 79177tert-Butyl bromoacetateHCID 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 70979588tert-butyl 2-(6-(4-chlorophenyl)-1-methyl-5-oxo-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepin-4-yl)acetateYield 51.4%

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 (200 mg, 0.62 mmol) in THF was added LiHMDS (0.9 mL, 0.9 mmol) at −78° C. The mixture was stirred at the same temperature for 1 h, and then tert-butyl 2-bromoacetate (180 mg, 0.92 mmol) was added, the mixture was warmed to room temperature and stirred overnight. NH4Cl aqueous (15 mL) was added, and then extracted with DCM (3×10 mL3). The combined organic layers were dried over Na2SO4, and the solvent was removed in vacuum. The residue was purified by column chromatography (silica-gel, DCM:MeOH=20:1) to give tert-butyl 2-(6-(4-chlorophenyl)-1-methyl-5-oxo-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepin-4-yl)acetate as a yellow solid (140 mg, 51.4%). LRMS (M+H)+: 324 m/z. 1H NMR (300 MHz, CD3OD): δ 1.46 (s, 9H), 2.72 (s, 3H), 3.08-3.15 (m, 1H), 3.31-3.39 (m, 1H), 4.10-4.15 (m, 1H), 7.15-7.23 (m, 3H), 7.40-7.43 (m, 2H), 7.50-7.54 (m, 2H), 7.74-7.79 (m, 1H).

Workup

  1. stirringstirred overnight
  2. extractionextracted with DCM (3×10 mL3)
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. customthe solvent was removed in vacuum
  5. customThe residue was purified by column chromatography (silica-gel, DCM:MeOH=20:1)

Sources & evidence

ORD record
ord-097a28f7a06443d39dbb879ba86fbd8f
Source dataset
uspto-grants-2016_08
Patent number
US09422292B2

Reaction notes

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