Potassium Carbonate → 10-[(2'-Methoxy-1,1'-biphenyl-4-yl)sulfonyl]-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide

HRID 2244262Notes

Reaction equation

HRID 2244262 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]2[C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=3[CH2:15][N:14]3[C:22]([C:25]([NH:27][CH2:28][C:29]4[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=4)=[O:26])=[CH:23][CH:24]=[C:13]3[CH2:12]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[CH3:35][O:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=1B(O)O.C(=O)([O-])[O-].[K+].[K+]>C(COC)OC>[CH3:35][O:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=1[C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]2[C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=3[CH2:15][N:14]3[C:22]([C:25]([NH:27][CH2:28][C:29]4[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=4)=[O:26])=[CH:23][CH:24]=[C:13]3[CH2:12]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27339582-Methoxyphenylboronic acidHCID 6869011210-[(4-Bromophenyl)sulfonyl]-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide

Product 1

HCID 1595246310-[(2'-Methoxy-1,1'-biphenyl-4-yl)sulfonyl]-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamideYield 114.3%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 10-[(4-bromophenyl)sulfonyl]-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide of Step C (0.500 g, 0.93 mmol), 2-methoxyphenylboronic acid (0.212 g, 1.40 mmol) and potassium carbonate (0.386 g, 2.79 mmol) in dimethoxyethane:water (8 mL:2 mL) was purged with nitrogen for 10 minutes. [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium[II] (38 mg, 0.0465 mmol) was then added and the reaction mixture heated to 90° C. for 21 hours. The cooled reaction mixture was partitioned between ethyl acetate (100 mL) and 1 M sodium hydroxide (100 mL). The separated organic phase was washed with water (100 mL) and brine (100 mL), dried over anhydrous magnesium sulfate, and concentrated in vacuo to give a brown syrup (0.60 g). Purification by flash chromatography using a solvent gradient of 0 to 3% methanol in dichloromethane gave the title compound (0.520 g, 99%) as a yellow foam.

Workup

  1. customwater (8 mL:2 mL) was purged with nitrogen for 10 minutes
  2. customThe cooled reaction mixture
  3. customwas partitioned between ethyl acetate (100 mL) and 1 M sodium hydroxide (100 mL)
  4. washThe separated organic phase was washed with water (100 mL) and brine (100 mL)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5803ecde887a46728e77783d7420ff33
Source dataset
uspto-grants-2010_03
Patent number
US07678787B2

Reaction notes

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