Dimethyl Sulfoxide → HCID 16039437, compound

HRID 639210Notes

Reaction equation

HRID 639210 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:26]=[CH:25][C:24]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=4[CH3:33])=[C:23]([CH3:34])[CH:22]=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.[CH3:41][O:42][C:43]1[CH:44]=[C:45]([CH:48]=[CH:49][CH:50]=1)[CH2:46][NH2:47]>C(#N)C>[CH3:34][C:23]1[CH:22]=[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:47][CH2:46][C:45]4[CH:48]=[CH:49][CH:50]=[C:43]([O:42][CH3:41])[CH:44]=4)=[O:4])=[CH:6][CH:7]=[C:8]3[CH2:9]2)=[O:20])[CH:26]=[CH:25][C:24]=1[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[CH3:33]

Participants

5

Reactant 3

HCID 679Dimethyl SulfoxideHCID 211563-MethoxybenzylamineHCID 160384712,2,2-Trichloro-1-{10-[(2,2'-dimethyl-1,1'-biphenyl-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}ethanone

Product 1

HCID 16039437HCID 16039437, compoundYield 59.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a suspension of 2,2,2-trichloro-1-{10-[(2,2′-dimethyl-1,1′-biphenyl-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}ethanone of Example 6 (0.538 g, 1.0 mmol) and dimethyl sulfoxide (0.35 mL, 4.9 mmol, 5 eq.) in acetonitrile (6 mL) was added 3-methoxybenzylamine (0.26 mL, 2.0 mmol, 2 eq.) and the reaction mixture was heated to reflux for 45 hours. The cooled reaction mixture was then concentrated in vacuo to remove acetonitrile. The oily residue was dissolved in ethyl acetate (25 mL), washed with 1N sodium hydroxide (25 mL), water (25 mL) and brine (25 mL), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to give the crude product (0.59 g) as a brown foam. Purification by flash chromatography using a solvent gradient of 20 to 40% ethyl acetate in hexane gave the title compound (330 mg, 59%) as a pale yellow solid. MS [(+)ESI, m/z]: 556 (M+H]+.HRMS [(+)ESI, m/z]: 556.25884 [M+H]+. Calcd for C36H34N3O3: 556.26002. Anal. Calcd for C36H33N3O3: C, 77.81; H, 5.99; N 7.56. Found: C, 77.50; H, 6.10; N 7.43.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureto reflux for 45 hours
  3. customThe cooled reaction mixture
  4. concentrationwas then concentrated in vacuo
  5. customto remove acetonitrile
  6. dissolutionThe oily residue was dissolved in ethyl acetate (25 mL)
  7. washwashed with 1N sodium hydroxide (25 mL), water (25 mL) and brine (25 mL)
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customto give the crude product (0.59 g) as a brown foam
  12. customPurification by flash chromatography

Sources & evidence

ORD record
ord-30277c29df5a42688ad761d22ad2e284
Source dataset
uspto-grants-2010_04
Patent number
US07691848B2

Reaction notes

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