Dimethyl Sulfoxide → HCID 15952465, compound

HRID 2244264Notes

Reaction equation

HRID 2244264 reaction equation
[C:1]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:6]=[CH:5][C:4]([CH2:7][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](=[O:27])C(Cl)(Cl)Cl)=[CH:20][CH:21]=[C:10]3[CH2:9]2)=[CH:3][CH:2]=1.CS(C)=O.[NH2:38][CH2:39][C:40]1[CH:41]=[N:42][CH:43]=[CH:44][CH:45]=1>C(#N)C>[C:1]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:2]=[CH:3][C:4]([CH2:7][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:38][CH2:39][C:40]4[CH:41]=[N:42][CH:43]=[CH:44][CH:45]=4)=[O:27])=[CH:20][CH:21]=[C:10]3[CH2:9]2)=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 679Dimethyl SulfoxideHCID 310183-PyridinemethanamineHCID 68687813HCID 68687813, compound

Product 1

HCID 15952465HCID 15952465, compoundYield 12%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 10-(1,1′-biphenyl-4-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine of Step A (0.93 g, 2.65 mmol) and N,N-dimethylaniline (0.51 mL, 3.98 mmol) in dry dichloromethane (30 mL) at 0° C. under nitrogen was added dropwise trichloroacetyl chloride (0.33 mL, 2.92 mmol). The ice bath was removed and the reaction mixture stirred at room temperature for 19 hours. The reaction mixture was then quenched by the addition of 2 M sodium hydroxide (30 mL) then partitioned between additional dichloromethane (75 mL) and 2 M sodium hydroxide (75 mL). The separated organic phase was washed with 2 M sodium hydroxide (75 mL) and water (75 mL), dried over anhydrous magnesium sulfate, and concentrated in vacuo to give a yellow syrup (2.12 g). Purification by flash chromatography using a solvent gradient of 1-5% ethyl acetate in hexane afforded 1-{10-[(1,1′-biphenyl)-4-ylmethyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-yl}-2,2,2-trichloroethanone (0.88 g, 67%) as a cream foam. To a solution of 1-{10-[(1,1′-biphenyl)-4-ylmethyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-yl}-2,2,2-trichloroethanone (0.4 g, 0.807 mmol) and dimethyl sulfoxide (0.29 mL, 4.034 mmol) in dry acetonitrile (5 mL) at room temperature under nitrogen was added 3-(aminomethyl)pyridine (0.17 mL, 1.613 mmol) and the reaction mixture was heated to reflux for 2 days. The cooled mixture was concentrated in vacuo, the semi-solid residue dissolved in ethyl acetate (50 mL), filtered and concentrated in vacuo to afford a dark brown syrup. Purification by flash chromatography using a solvent gradient of 0.5 to 3% methanol in dichloromethane afforded an orange semi-solid that was crystallized from dichloromethane/hexane to give the title compound (0.047 g, 12%) as a cream solid, m.p. 161-165° C. (dec.).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureto reflux for 2 days
  3. concentrationThe cooled mixture was concentrated in vacuo
  4. dissolutionthe semi-solid residue dissolved in ethyl acetate (50 mL)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto afford a dark brown syrup
  8. customPurification by flash chromatography
  9. customafforded an orange semi-solid
  10. customthat was crystallized from dichloromethane/hexane

Sources & evidence

ORD record
ord-cdb9e2c580204feaadc0baf2c5483b23
Source dataset
uspto-grants-2010_03
Patent number
US07678787B2

Reaction notes

Loading…