Diisopropylethylamine → (R)-1-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1-methyl-1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-(3,4-dichlorophenyl)pyrrolidine

HRID 323223Notes

Reaction equation

HRID 323223 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:28]=[C:29]([O:33][CH3:34])[C:30]=1[O:31][CH3:32])[C:6]([N:8]1[CH2:12][CH2:11][C@@:10]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([Cl:27])[CH:21]=2)([CH2:13][CH2:14]OS(C)(=O)=O)[CH2:9]1)=[O:7].[CH3:35][N:36]1[C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][C:39]=2[N:38]=[C:37]1[NH:45][CH:46]1[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]1.C(N(CC)C(C)C)(C)C.CO.C(OCC)(=O)C>C(#N)C.C(OCC)(=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:28]=[C:29]([O:33][CH3:34])[C:30]=1[O:31][CH3:32])[C:6]([N:8]1[CH2:12][CH2:11][C@:10]([CH2:13][CH2:14][N:49]2[CH2:50][CH2:51][CH:46]([NH:45][C:37]3[N:36]([CH3:35])[C:40]4[CH:41]=[CH:42][CH:43]=[CH:44][C:39]=4[N:38]=3)[CH2:47][CH2:48]2)([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([Cl:27])[CH:21]=2)[CH2:9]1)=[O:7]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 10896745(S)-1-(3,4,5-trimethoxybenzoyl)-3-(3,4-dichlorophenyl)-3-(2-methanesulfonyloxyethyl)pyrrolidineHCID 21584119Ethylacetate methanolHCID 22009124(1-methyl-1H-benzimidazol-2-yl)(piperidin-4-yl)amine

Product 1

HCID 53998673(R)-1-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1-methyl-1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-(3,4-dichlorophenyl)pyrrolidine

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

Combine (S)-1-(3,4,5-trimethoxybenzoyl)-3-(3,4-dichlorophenyl)-3-(2-methanesulfonyloxyethyl)pyrrolidine (0.34 g, 0.63 mmol) and (1-methyl-1H-benzimidazol-2-yl)(piperidin-4-yl)amine (0.24 g, 1.0 mmol), and N,N-diisopropylethylamine (0.26 mL, 2.4 mmol) in acetonitrile (25 mL). Heat to reflux. After 2 days, cool and dilute the reaction mixture with ethyl acetate. Extract twice with 1/1 brine/water, saturated aqueous sodium bicarbonate, and brine. Dry the organic layer over Na2SO4, filter, and concentrate in vacuo to obtain a residue. Chromatograph the residue on a short column of silica gel eluting sequentially with ethyl acetate and then 50% methanol/ethyl acetate to give a residue. Partition the residue between ethyl acetate and water. Separate the layers and extract the organic layer with water. Dry the organic layer over Na2SO4, filter, and concentrate in vacuo to give the title compound: Rf=0.24 (silica gel, 30% methanol/ethyl acetate).

Workup

  1. temperatureHeat to reflux
  2. temperaturecool
  3. extractionExtract twice with 1/1 brine/water, saturated aqueous sodium bicarbonate, and brine
  4. dry with materialDry the organic layer over Na2SO4
  5. filtrationfilter
  6. concentrationconcentrate in vacuo
  7. customto obtain a residue
  8. customPartition the residue between ethyl acetate and water
  9. customSeparate the layers
  10. extractionextract the organic layer with water
  11. dry with materialDry the organic layer over Na2SO4
  12. filtrationfilter
  13. concentrationconcentrate in vacuo

Sources & evidence

ORD record
ord-65c21d02873f49bdba1f65c47a4c97fb
Source dataset
uspto-grants-2001_04
Patent number
US06211199B1

Reaction notes

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