Dimethyl Sulfoxide → 10-[(2'-Methyl-1,1'-biphenyl-3-yl)carbonyl]-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide

HRID 2244228Notes

Reaction equation

HRID 2244228 reaction equation
ClC(Cl)(Cl)[C:3]([C:5]1[N:14]2[C:8]([CH2:9][N:10]([C:19]([C:21]3[CH:22]=[C:23]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=4[CH3:33])[CH:24]=[CH:25][CH:26]=3)=[O:20])[C:11]3[CH:18]=[CH:17][CH:16]=[CH:15][C:12]=3[CH2:13]2)=[CH:7][CH:6]=1)=[O:4].CS(C)=O.[NH2:40][CH2:41][C:42]1[CH:43]=[N:44][CH:45]=[CH:46][CH:47]=1>C(#N)C>[CH3:33][C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=1[C:23]1[CH:24]=[CH:25][CH:26]=[C:21]([C:19]([N:10]2[C:11]3[CH:18]=[CH:17][CH:16]=[CH:15][C:12]=3[CH2:13][N:14]3[C:5]([C:3]([NH:40][CH2:41][C:42]4[CH:43]=[N:44][CH:45]=[CH:46][CH:47]=4)=[O:4])=[CH:6][CH:7]=[C:8]3[CH2:9]2)=[O:20])[CH:22]=1

Participants

5

Reactant 3

HCID 679Dimethyl SulfoxideHCID 310183-PyridinemethanamineHCID 686873312,2,2-Trichloro-1-{10-[(2'-methyl-1,1'-biphenyl-3-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}ethanone

Product 1

HCID 6868637910-[(2'-Methyl-1,1'-biphenyl-3-yl)carbonyl]-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamideYield 77.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 2,2,2-trichloro-1-{10-[(2′-methyl-1,1′-biphenyl-3-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}ethanone of Step C (0.600 g, 1.1 mmol) and dimethyl sulfoxide (0.41 mL, 5.8 mmol) in dry acetonitrile (5.5 mL) at room temperature under nitrogen was added 3-(aminomethyl)pyridine (0.23 mL, 2.2 mmol) and the reaction mixture heated to reflux for 45 hours. The cooled reaction mixture was concentrated in vacuo, the oily residue redissolved in ethyl acetate (25 mL), washed with 1 M sodium hydroxide (25 mL), water (25 mL) and brine (25 mL), dried over anhydrous magnesium sulfate, and concentrated in vacuo to give a pale orange foam. Purification by flash chromatography using ethyl acetate as solvent afforded a pale yellow foam that was recrystallized from ethyl acetate/diethyl ether/hexane to give the title compound (0.435 g, 74%) as an off-white crystalline solid.

Workup

  1. temperaturethe reaction mixture heated
  2. temperatureto reflux for 45 hours
  3. customThe cooled reaction mixture
  4. concentrationwas concentrated in vacuo
  5. dissolutionthe oily residue redissolved in ethyl acetate (25 mL)
  6. washwashed with 1 M sodium hydroxide (25 mL), water (25 mL) and brine (25 mL)
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated in vacuo
  9. customto give a pale orange foam
  10. customPurification by flash chromatography
  11. customafforded a pale yellow foam that
  12. customwas recrystallized from ethyl acetate/diethyl ether/hexane

Sources & evidence

ORD record
ord-9ceab5eeac5444ec85cb170f11a3e32b
Source dataset
uspto-grants-2010_03
Patent number
US07678787B2

Reaction notes

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