Dimethyl Sulfoxide → 10-[(4-Bromophenyl)sulfonyl]-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide

HRID 2244261Notes

Reaction equation

HRID 2244261 reaction equation
[Br: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](=[O:30])C(Cl)(Cl)Cl)=[CH:23][CH:24]=[C:13]3[CH2:12]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.CS(C)=O.[NH2:35][CH2:36][C:37]1[CH:38]=[N:39][CH:40]=[CH:41][CH:42]=1>C(#N)C>[Br: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:35][CH2:36][C:37]4[CH:38]=[N:39][CH:40]=[CH:41][CH:42]=4)=[O:30])=[CH:23][CH:24]=[C:13]3[CH2:12]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 679Dimethyl SulfoxideHCID 310183-PyridinemethanamineHCID 68686100HCID 68686100, compound

Product 1

HCID 6869011210-[(4-Bromophenyl)sulfonyl]-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamideYield 91%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 1-{10-[(4-bromophenyl)sulfonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}-2,2,2-trichloroethanone of Step B (1.80 g, 3.297 mmol) and dimethyl sulfoxide (1.17 mL, 16.487 mmol) in dry acetonitrile (30 mL) at room temperature under nitrogen was added 3-(aminomethyl)pyridine (0.67 mL, 6.595 mmol) and the reaction mixture heated to reflux for 20 hours. The cooled reaction mixture was concentrated in vacuo, the oily residue dissolved in ethyl acetate (100 mL), washed with 1M sodium hydroxide (2×100 mL), water (100 mL) and brine (100 mL), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to give a yellow foam. Purification by flash chromatography using a solvent gradient of 0 to 3% methanol in dichloromethane gave the title compound (1.61 g, 91%) as a yellow foam.

Workup

  1. temperaturethe reaction mixture heated
  2. temperatureto reflux for 20 hours
  3. customThe cooled reaction mixture
  4. concentrationwas concentrated in vacuo
  5. dissolutionthe oily residue dissolved in ethyl acetate (100 mL)
  6. washwashed with 1M sodium hydroxide (2×100 mL), water (100 mL) and brine (100 mL)
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto give a yellow foam
  11. customPurification by flash chromatography

Sources & evidence

ORD record
ord-8153b16c282645c5ab02a0b6241eb7c4
Source dataset
uspto-grants-2010_03
Patent number
US07678787B2

Reaction notes

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