Potassium Carbonate → 10-[(2'-Methyl-1,1'-biphenyl-3-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine

HRID 2244226Notes

Reaction equation

HRID 2244226 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][CH:23]=1)[C:5]([N:7]1[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=2[CH2:11][N:10]2[CH:18]=[CH:19][CH:20]=[C:9]2[CH2:8]1)=[O:6].[C:24]1([CH3:33])[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1B(O)O.C(=O)([O-])[O-].[K+].[K+]>COCCOC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:33][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[C:2]1[CH:23]=[CH:22][CH:21]=[C:4]([C:5]([N:7]2[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[CH2:11][N:10]3[CH:18]=[CH:19][CH:20]=[C:9]3[CH2:8]2)=[O:6])[CH:3]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27332672-Methylphenyl boronic acidHCID 6868783410-(3-Bromobenzoyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine

Product 1

HCID 6868820210-[(2'-Methyl-1,1'-biphenyl-3-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepineYield 85%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of 10-(3-bromobenzoyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine of Step A (2.0 g, 5.4 mmol), o-tolylboronic acid (0.8 g, 5.9 mmol) and potassium carbonate (2.4 g, 17.7 mmol) in ethylene glycol dimethyl ether: water (20 mL: 5 mL) was purged with nitrogen for 1 hour. [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium [II] (0.22 g, 0.26 mmol) was added and the reaction mixture heated to 75° C. with vigorous stirring for 16 hours. The cooled reaction mixture was then filtered through Celite and the cake washed with dichloromethane (100 mL). The organic phase was separated, washed with 1 M sodium hydroxide (100 mL) and brine (100 mL), dried over anhydrous potassium carbonate and concentrated in vacuo to give the crude product (2.3 g) as a dark brown solid. Purification by flash chromatography using a solvent gradient of 40% to 100% dichloromethane in hexane afforded the title compound (1.7 g, 85%) as a white solid.

Workup

  1. customwater (20 mL: 5 mL) was purged with nitrogen for 1 hour
  2. customThe cooled reaction mixture
  3. filtrationwas then filtered through Celite
  4. washthe cake washed with dichloromethane (100 mL)
  5. customThe organic phase was separated
  6. washwashed with 1 M sodium hydroxide (100 mL) and brine (100 mL)
  7. dry with materialdried over anhydrous potassium carbonate
  8. concentrationconcentrated in vacuo
  9. customto give the crude product (2.3 g) as a dark brown solid
  10. customPurification by flash chromatography

Sources & evidence

ORD record
ord-45a4321ec20a4bf0b4f38e716ce289b7
Source dataset
uspto-grants-2010_03
Patent number
US07678787B2

Reaction notes

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