Diisopropylethylamine → (2R)-1-Methoxy-3-{4-[(10-{[2-methyl-2'-trifluoromethyl-[1,1'-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl)carbonyl]piperazin-1-yl}propan-2-ol

HRID 2184440Notes

Reaction equation

HRID 2184440 reaction equation
Cl.[CH3:2][C:3]1[CH:8]=[C:7]([C:9]([N:11]2[C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=3[CH2:15][N:14]3[C:22]([C:25]([N:27]4[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]4)=[O:26])=[CH:23][CH:24]=[C:13]3[CH2:12]2)=[O:10])[CH:6]=[CH:5][C:4]=1[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[C:39]([F:42])([F:41])[F:40].C(N(CC)C(C)C)(C)C.[CH3:52][O:53][CH2:54][C@@H:55]1[O:57][CH2:56]1>CO>[CH3:52][O:53][CH2:54][C@H:55]([OH:57])[CH2:56][N:30]1[CH2:29][CH2:28][N:27]([C:25]([C:22]2[N:14]3[C:13]([CH2:12][N:11]([C:9]([C:7]4[CH:6]=[CH:5][C:4]([C:33]5[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=5[C:39]([F:40])([F:42])[F:41])=[C:3]([CH3:2])[CH:8]=4)=[O:10])[C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=4[CH2:15]3)=[CH:24][CH:23]=2)=[O:26])[CH2:32][CH2:31]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 2734441(2R)-2-(Methoxymethyl)oxiraneHCID 2194778410,11-Dihydro-10-[[2-methyl-2'-trifluoromethyl-[1,1'-biphenyl]-4-yl]carbonyl]-3-(1-piperazinylcarbonyl)-5h-pyrrolo[2,1-c][1,4]benzodiazepine hydrochloride salt

Product 1

HCID 10189701(2R)-1-Methoxy-3-{4-[(10-{[2-methyl-2'-trifluoromethyl-[1,1'-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl)carbonyl]piperazin-1-yl}propan-2-olYield 73.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 10,11-dihydro-10-[[2-methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]carbonyl]-3-(1-piperazinylcarbonyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepine hydrochloride salt of Example 5, Step B (0.50 g, 0.84 mmol) and N,N-diisopropylethyl amine (0.16 mL, 0.92 mmol) in methanol (5 mL) was added (R)-(−)-glycidyl methyl ether (0.11 mL, 1.22 mmol). The reaction mixture was heated to 60° C. overnight then cooled and concentrated in vacuo. The residue was partitioned between dichloromethane and water. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a white foam. Purification by flash chromatography on silica gel using a solvent system of 3% methanol in chloroform provided 0.40 g of title product as a white foam.

Workup

  1. temperaturethen cooled
  2. concentrationconcentrated in vacuo
  3. customThe residue was partitioned between dichloromethane and water
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give a white foam
  8. customPurification by flash chromatography on silica gel using a solvent system of 3% methanol in chloroform

Sources & evidence

ORD record
ord-739f3be35043477b93e83b468b87b5f3
Source dataset
uspto-grants-2005_05
Patent number
US06900200B2

Reaction notes

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