Dimethyl Sulfoxide → N-[(1R)-2-Hydroxy-1-phenylethyl]-10-[(2'-methoxy-1,1'-biphenyl-4-YL)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-C][1,4]benzodiazepine-3-carboxamide

HRID 639205Notes

Reaction equation

HRID 639205 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].[NH2:37][C@H:38]([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[CH2:39][OH:40].CS(C)=O.C(N(CC)CC)C>C(#N)C.ClCCl>[OH:40][CH2:39][C@H:38]([NH:37][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])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 2724025(R)-beta-aminophenethyl alcoholHCID 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}ethanone

Product 1

HCID 16038410N-[(1R)-2-Hydroxy-1-phenylethyl]-10-[(2'-methoxy-1,1'-biphenyl-4-YL)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-C][1,4]benzodiazepine-3-carboxamideYield 51.5%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
82.5 °C

Procedure

A mixture of 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 of Example 1 (0.517 g, 0.985 mmole) and (R)-(−)-2-amino-2-phenylethanol (0.276 g, 20 mmole), dimethylsulfoxide (2.8 mmole) and triethylamine (0.213 g, 2.1 mmole) in acetonitrile (10 mL) was heated at 80-85° C. for 22 hours. The residue left upon removal of the solvent was taken up in 15 mL of dichloromethane, washed with brine, dried over anhydrous magnesium sulfate and concentrated to give a tan solid. Purification by flash chromatography on silica gel Merck-60 using a gradient of 0 to 25% ethyl acetate in dichloromethane provided a light yellow solid (0.283 g). Recrystallization from ethyl acetate/hexane gave the title compound as off-white needles, m.p. 195-196° C. MS [(+)ESI, m/z]: 558.14 [M+H]+

Workup

  1. waitThe residue left upon removal of the solvent
  2. washwashed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated
  5. customto give a tan solid
  6. customPurification by flash chromatography on silica gel Merck-60

Sources & evidence

ORD record
ord-621b7f1e320746a683cbb8d9cff1ab17
Source dataset
uspto-grants-2010_04
Patent number
US07691848B2

Reaction notes

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