Water → 1-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1-(3-(4-fluorophenoxy)propyl)-1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-(3,4-difluorophenyl)pyrrolidine

HRID 323324Notes

Reaction equation

HRID 323324 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:39]=[C:40]([O:44][CH3:45])[C:41]=1[O:42][CH3:43])[C:6]([N:8]1[CH2:12][CH2:11][C:10]([CH2:21][CH2:22][N:23]2[CH2:28][CH2:27][CH:26]([NH:29][C:30]3[NH:34][C:33]4[CH:35]=[CH:36][CH:37]=[CH:38][C:32]=4[N:31]=3)[CH2:25][CH2:24]2)([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[C:15]([F:20])[CH:14]=2)[CH2:9]1)=[O:7].Cl[CH2:47][CH2:48][CH2:49][O:50][C:51]1[CH:56]=[CH:55][C:54]([F:57])=[CH:53][CH:52]=1.[OH-].[Na+].O>[Cl-].C([N+](CC)(CC)CC1C=CC=CC=1)C.C(OCC)(=O)C.CO.C(OCC)(=O)C.ClCCl>[CH3:45][O:44][C:40]1[CH:39]=[C:5]([CH:4]=[C:3]([O:2][CH3:1])[C:41]=1[O:42][CH3:43])[C:6]([N:8]1[CH2:12][CH2:11][C:10]([CH2:21][CH2:22][N:23]2[CH2:28][CH2:27][CH:26]([NH:29][C:30]3[N:31]([CH2:47][CH2:48][CH2:49][O:50][C:51]4[CH:52]=[CH:53][C:54]([F:57])=[CH:55][CH:56]=4)[C:32]4[CH:38]=[CH:37][CH:36]=[CH:35][C:33]=4[N:34]=3)[CH2:25][CH2:24]2)([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[C:15]([F:20])[CH:14]=2)[CH2:9]1)=[O:7]

Participants

9

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 743911-(3-Chloropropoxy)-4-fluorobenzeneHCID 220092161-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-(3,4-difluorophenyl)pyrrolidine

Product 1

HCID 98536791-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1-(3-(4-fluorophenoxy)propyl)-1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-(3,4-difluorophenyl)pyrrolidine

Reagents, catalysts & solvents 4

HCID 66133Benzyl triethylammonium chlorideCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 21584119Ethylacetate methanolSolvent

Conditions

Temperature
35 °C

Procedure

Combine 1-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-(3,4-difluorophenyl)pyrrolidine (0.48 g, 0.78 mmol), 1-chloro-3-(4-fluorophenoxy)propane (0.15 g, 0.78 mmol), triethylbenzyl ammonium chloride (0.01 g), sodium hydroxide (2.0 g), water (2 mL), and dichloromethane (4 mL). Heat to about 35° C. After 18 hours, add ethyl acetate (100 mL) and separate the layers. Extract the organic layer with aqueous saturated sodium bicarbonate and brine. Dry the organic layer over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting with 3/1 ethyl acetate/methanol to give the title compound. Rf=0.20 (silica gel, 3/1 ethyl acetate/methanol).

Workup

  1. customseparate the layers
  2. extractionExtract the organic layer with aqueous saturated sodium bicarbonate and brine
  3. dry with materialDry the organic layer over Na2SO4
  4. filtrationfilter
  5. customevaporate in vacuo
  6. customto give a residue

Sources & evidence

ORD record
ord-1f5137b0feba430db28ca02113afe852
Source dataset
uspto-grants-2001_04
Patent number
US06211199B1

Reaction notes

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