Dimethyl Sulfoxide → HCID 10301874, compound

HRID 2244202Notes

Reaction equation

HRID 2244202 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.[NH2:41][CH2:42][C:43]1[CH:44]=[N:45][CH:46]=[CH:47][CH:48]=1.C(OCC)C>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:41][CH2:42][C:43]4[CH:44]=[N:45][CH:46]=[CH:47][CH:48]=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

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 3283Diethyl EtherHCID 310183-PyridinemethanamineHCID 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 10301874HCID 10301874, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution 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 Step D (8.0 g, 15 mmol) and dimethyl sulfoxide (5.3 mL, 75 mmol) in dry acetonitrile (90 mL) at room temperature under nitrogen was added 3-(aminomethyl)pyridine (3.1 mL, 30 mmol) and the reaction mixture was heated to reflux for 48 hours. The cooled mixture was concentrated in vacuo, the oily residue redissolved in ethyl acetate (400 mL), washed with 1M sodium hydroxide (100 mL) and brine (100 mL), dried over anhydrous magnesium sulfate, and concentrated in vacuo to give a red foam. Purification by flash chromatography using a solvent gradient of 50 to 100% ethyl acetate in hexane gave a pale yellow foam. Trituration with hot diethyl ether (150 mL) afforded the title compound (5.9 g, 75%) as a pale yellow solid, m.p. 147-149° C. Alternatively, the title compound could be purified by HPLC (normal phase, Luna CN bonded packing) and crystallized from ethyl acetate/hexane, m.p. 148-150° C.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureto reflux for 48 hours
  3. concentrationThe cooled mixture was concentrated in vacuo
  4. dissolutionthe oily residue redissolved in ethyl acetate (400 mL)
  5. washwashed with 1M sodium hydroxide (100 mL) and brine (100 mL)
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. customto give a red foam
  9. customPurification by flash chromatography
  10. customgave a pale yellow foam

Sources & evidence

ORD record
ord-20ce7c2988674ec6bad0965610f02633
Source dataset
uspto-grants-2010_03
Patent number
US07678787B2

Reaction notes

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