Sodium Carbonate → HCID 10143682, compound

HRID 2244245Notes

Reaction equation

HRID 2244245 reaction equation
I[C:2]1[CH:33]=[CH:32][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[C:19]([C:22]([NH:24][CH2:25][C:26]4[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=4)=[O:23])=[CH:20][CH:21]=[C:10]3[CH2:9]2)=[O:7])=[CH:4][C:3]=1[CH3:34].[CH3:35][O:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:35][O:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=1[C:2]1[CH:33]=[CH:32][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[C:19]([C:22]([NH:24][CH2:25][C:26]4[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=4)=[O:23])=[CH:20][CH:21]=[C:10]3[CH2:9]2)=[O:7])=[CH:4][C:3]=1[CH3:34]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27339582-Methoxyphenylboronic acidHCID 15952466HCID 15952466, compound

Product 1

HCID 10143682HCID 10143682, compoundYield 119.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 10-(4-iodo-3-methylbenzoyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide of Example 74, Step C (0.200 g, 0.356 mmol), and 2-methoxyphenylboronic acid (0.081 g, 0.533 mmol) in acetonitrile (3 mL) was added a 0.4 M aqueous sodium carbonate solution (3 mL) and the mixture purged with nitrogen for 10 minutes. Tetrakis(triphenylphosphine)palladium(0) (0.021 g, 0.018 mmol) was then added and the reaction mixture heated to 90° C. for 4 hours. The cooled reaction mixture was partitioned between ethyl acetate (50 mL) and 2 M sodium hydroxide (50 mL). The organic phase was separated, washed with 2 M sodium hydroxide (50 mL), water (50 mL) and brine (50 mL), dried over amnhydrous magnesium sulfate, and concentrated in vacuo to give a yellow syrup (0.23 g). Purification by flash chromatography using a solvent gradient of 1 to 5% methanol in dichloromethane gave a colorless glass that was recrystallized from dichloromethane/hexane to afford the title compound (0.181 g, 94%) as a white solid, m.p. 119-124° C.

Workup

  1. customthe mixture purged with nitrogen for 10 minutes
  2. customThe cooled reaction mixture
  3. customwas partitioned between ethyl acetate (50 mL) and 2 M sodium hydroxide (50 mL)
  4. customThe organic phase was separated
  5. washwashed with 2 M sodium hydroxide (50 mL), water (50 mL) and brine (50 mL)
  6. dry with materialdried over amnhydrous magnesium sulfate
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f0ea2fff13c54b31b2191790a72b967f
Source dataset
uspto-grants-2010_03
Patent number
US07678787B2

Reaction notes

Loading…