Dimethyl Sulfoxide → HCID 68687112, compound

HRID 2244208Notes

Reaction equation

HRID 2244208 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[O:33][CH3:34])=[CH:23][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].Cl.Cl.Cl.[N:40]1[CH:45]=[CH:44][CH:43]=[C:42]([CH:46]([N:49]2[CH2:53][CH2:52][CH2:51][CH2:50]2)[CH2:47][NH2:48])[CH:41]=1.C(N(CC)CC)C.CS(C)=O>C(#N)C>[CH3:34][O:33][C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=1[C:24]1[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:48][CH2:47][CH:46]([C:42]4[CH:41]=[N:40][CH:45]=[CH:44][CH:43]=4)[N:49]4[CH2:53][CH2:52][CH2:51][CH2:50]4)=[O:4])=[CH:6][CH:7]=[C:8]3[CH2:9]2)=[O:20])=[CH:22][CH:23]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 160384072,2,2-trichloro-1-{10-[(2'-methoxy-1,1'-biphenyl-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}ethanoneHCID 68688415HCID 68688415, compound

Product 1

HCID 68687112HCID 68687112, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

The title compound was prepared according to the procedure Example 6, Step D, from 2,2,2-trichloro-1-{10-[(2′-methoxy-1,1′-biphenyl-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}ethanone (1.21 g, 2.25 mmol), 2-(3-pyridyl)-2-pyrrolidinylethyl amine trihydrochloride (0.450 g, 1.5 mmol), triethylamine (5 equivalents), dimethylsulfoxide (0.540 mL) and acetonitrile (28 mL). The crude material was flash chromatographed over silica gel Merck-60 using a gradient of methanol (1-5%) in dichloromethane containing 0.2% ammonium hydroxide, to provide a brown foam. The material was further purified by preparative HPLC (40:60 acetonitrile:water containing 0.1% formic acid; Primesphere 10 C18, 250×50 mm column; flow 90 mL/min). The solution was brought to pH 8 with concentrated ammonium hydroxide prior to concentration to small volume in vacuo. The residue was redissolved in dichloromethane, dried over anhydrous potassium carbonate and evaporated to dryness to provide an off-white foam (0.560 g). This material was sonicated with hexane (containing a few drops of ethyl acetate). The resulting off-white powder was collected and dried (0.442 g).

Workup

  1. customchromatographed over silica gel Merck-60
  2. customto provide a brown foam
  3. customThe material was further purified by preparative HPLC (40:60 acetonitrile
  4. concentrationto concentration to small volume in vacuo
  5. dissolutionThe residue was redissolved in dichloromethane
  6. dry with materialdried over anhydrous potassium carbonate
  7. customevaporated to dryness

Sources & evidence

ORD record
ord-f919e1ec99b34ba49d78646fb38c32e5
Source dataset
uspto-grants-2010_03
Patent number
US07678787B2

Reaction notes

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