Cesium carbonate → 6-(4-Chlorophenyl)-1-methyl-5,6-dihydrospiro[benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepine-4,1'-cyclopropane]

HRID 1485433Notes

Reaction equation

HRID 1485433 reaction equation
[CH3:1][C:2]1[N:6]2[C:7]3[CH:17]=[CH:16][CH:15]=[CH:14][C:8]=3[NH:9][CH2:10][C:11]3([CH2:13][CH2:12]3)[C:5]2=[N:4][N:3]=1.[Cl:18][C:19]1[CH:24]=[CH:23][C:22](I)=[CH:21][CH:20]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([N:9]2[CH2:10][C:11]3([CH2:12][CH2:13]3)[C:5]3=[N:4][N:3]=[C:2]([CH3:1])[N:6]3[C:7]3[CH:17]=[CH:16][CH:15]=[CH:14][C:8]2=3)=[CH:21][CH:20]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 125101-Chloro-4-iodobenzeneHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 710035961-Methyl-5,6-dihydrospiro[benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepine-4,1'-cyclopropane]

Product 1

HCID 709792096-(4-Chlorophenyl)-1-methyl-5,6-dihydrospiro[benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepine-4,1'-cyclopropane]Yield 4.8%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

A solution of 1-methyl-5,6-dihydrospiro[benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepine-4,1′-cyclopropane] (111 mg, 0.49 mmol), 1-chloro-4-iodobenzene (468 mg, 2.0 mmol), tris(dibenzylideneacetone)dipalladium(0) (35 mg, 0.049 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (40 mg, 0.098 mmol) and cesium carbonate anhydrous (320 mg, 0.98 mmol) in toluene (10 mL) was heated to 110° C., and maintained at the same temperature for 12 hours. The reaction mixture was concentrated, added with water (20 mL), extracted with ethyl acetate (20 mL). The organic phase was separated, and concentrated to give a crude product, which was purified by preparative-TLC (silica-gel, dichloromethane/methanol=30:1) to afford 6-(4-chlorophenyl)-1-methyl-5,6-dihydrospiro[benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepine-4,1′-cyclopropane] (8 mg, 4.8%).

Workup

  1. temperaturemaintained at the same temperature for 12 hours
  2. concentrationThe reaction mixture was concentrated
  3. additionadded with water (20 mL)
  4. extractionextracted with ethyl acetate (20 mL)
  5. customThe organic phase was separated
  6. concentrationconcentrated
  7. customto give a crude product, which
  8. customwas purified by preparative-TLC (silica-gel, dichloromethane/methanol=30:1)

Sources & evidence

ORD record
ord-d44b8350cd4744de97108c239d54d8cd
Source dataset
uspto-grants-2016_08
Patent number
US09422292B2

Reaction notes

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