Sodium Carbonate → (10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-[3-methoxy-2'-methyl-[1,1'-biphenyl]-4-yl]-methanone

HRID 2184464Notes

Reaction equation

HRID 2184464 reaction equation
I[C:2]1[CH:23]=[CH:22][C:5]([C:6]([N:8]2[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[CH2:12][N:11]3[CH:19]=[CH:20][CH:21]=[C:10]3[CH2:9]2)=[O:7])=[C:4]([O:24][CH3:25])[CH:3]=1.[CH3:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.[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>[CH:21]1[CH:20]=[CH:19][N:11]2[CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[N:8]([C:6]([C:5]3[CH:22]=[CH:23][C:2]([C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=4[CH3:26])=[CH:3][C:4]=3[O:24][CH3:25])=[O:7])[CH2:9][C:10]=12

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27332672-Methylphenyl boronic acidHCID 21947920(4-Iodo-2-methoxyphenyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)-ylmethanone

Product 1

HCID 21947713(10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-[3-methoxy-2'-methyl-[1,1'-biphenyl]-4-yl]-methanoneYield 89.6%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 10-(4-iodo-2-methoxybenzoyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine of Step C (1.8 g, 4.1 mmol), 2-methylphenyl boronic acid (0.55 g, 4.1 mmol) and sodium carbonate (1.9 g, 17.9 mmol) in toluene:ethanol: water (20 mL:10 mL:10 mL) was purged with nitrogen for 1 hour. After addition of the tetrakis(triphenylphosphine) palladium(0) catalyst (0.24 g, 0.21 mmol), the reaction mixture was heated at 100° C. overnight. After cooling, the reaction was filtered through Celite and the cake washed with ethyl acetate. The organic layer was washed with water, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a brown oil. Purification by flash chromatography on silica gel using a solvent system of 20% ethyl acetate in hexane provided 1.5 g of title product as a white foam, which was redissolved in dichloromethane and evaporated to dryness in vacuo prior to use in the next step.

Workup

  1. customethanol: water (20 mL:10 mL:10 mL) was purged with nitrogen for 1 hour
  2. temperatureAfter cooling
  3. filtrationthe reaction was filtered through Celite
  4. washthe cake washed with ethyl acetate
  5. washThe organic layer was washed with water
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a brown oil
  10. customPurification by flash chromatography on silica gel using a solvent system of 20% ethyl acetate in hexane

Sources & evidence

ORD record
ord-1a8228a4e25e40fda26c3a58e32df453
Source dataset
uspto-grants-2005_05
Patent number
US06900200B2

Reaction notes

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