Toluene → (2-Methyl-4-thiophen-2-yl-phenyl)-(5,11-dihydro-pyrido[2,3-b][1,5]benzodiazepin-10-yl)-methanone

HRID 1387308Notes

Reaction equation

HRID 1387308 reaction equation
BrC1C=CC(C([N:10]2[C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=3[NH:14][C:13]3[N:21]=[CH:22][CH:23]=[CH:24][C:12]=3[CH2:11]2)=O)=C(C)C=1.[S:26]1[CH:30]=[CH:29][CH:28]=[C:27]1B(O)O.[C:34](=[O:37])([O-])[O-].[Na+].[Na+].B(O)O.[C:43]1([CH3:49])[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>C(O)C.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:49][C:43]1[CH:48]=[C:47]([C:27]2[S:26][CH:30]=[CH:29][CH:28]=2)[CH:46]=[CH:45][C:44]=1[C:34]([C:20]1[C:15]2[NH:14][C:13]3[N:21]=[CH:22][CH:23]=[CH:24][C:12]=3[CH2:11][NH:10][C:16]=2[CH:17]=[CH:18][CH:19]=1)=[O:37]

Participants

9

Reactant 5

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 61668Boronic AcidHCID 27339602-Thiopheneboronic acidHCID 15547049(4-Bromo-2-methyl-phenyl)-(5,11-dihydro-pyrido[2,3-b][1,5]benzodiazepin-6-yl)-methanone

Product 1

HCID 21696872(2-Methyl-4-thiophen-2-yl-phenyl)-(5,11-dihydro-pyrido[2,3-b][1,5]benzodiazepin-10-yl)-methanone

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Procedure

To a solution of (4-bromo-2-methyl-phenyl)-(5,11-dihydro-pyrido[2,3-b][1,5]benzodiazepin-6-yl)-methanone (0.5 g, 1.27 mmol) of Step A, thiophene-2-boronic acid (0.167 g, 1.30 mmol) and sodium carbonate (0.595 g, 5.6 mmol) in toluene (20 mL), ethanol (10 mL) and water (10 mL) under nitrogen was added tetrakis (triphenylphosphine) palladium(0) catalyst (0.066 g, 0.057 mmol). The mixture was heated at reflux for 19 hours. Additional boronic acid (0.170 g, 1.30 mmol) and catalyst (0.050 g, 0.043 mmol) were added and reflux resumed for 3 hours. After stirring overnight at room temperature, the mixture was filtered through Celite and the cake washed with ethyl acetate. The combined organic layers were washed with water, dried over anhydrous sodium sulfate, and evaporated to dryness. The residue was dissolved in dichloromethane, absorbed onto a silica Merck-60 flash column and eluted with an ethyl acetate- hexane gradient (from 30 to 50%) to provide the title compound (0.29 g) as a foam, which crystallized as a white solid by trituration with diethyl ether/ hexane, m.p. 118-120° C.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 19 hours
  3. temperaturereflux
  4. filtrationthe mixture was filtered through Celite
  5. washthe cake washed with ethyl acetate
  6. washThe combined organic layers were washed with water
  7. dry with materialdried over anhydrous sodium sulfate
  8. customevaporated to dryness
  9. dissolutionThe residue was dissolved in dichloromethane
  10. customabsorbed onto a silica Merck-60 flash column
  11. washeluted with an ethyl acetate- hexane gradient (from 30 to 50%)

Sources & evidence

ORD record
ord-c6a85369f63b4d8d9219c33e217ba770
Source dataset
uspto-grants-2001_07
Patent number
US06268360B1

Reaction notes

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