Triethylamine → 1-(2-methoxy-5-(1H-tetrazol-1-yl)benzoyl)-3-(2-(4-(1-(2-(isopropyloxy)ethyl)-1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-phenylpyrrolidine

HRID 323476Notes

Reaction equation

HRID 323476 reaction equation
[CH3:1][O:2][C:3]1[CH:28]=[CH:27][C:26]([N:29]2[CH:33]=[N:32][N:31]=[N:30]2)=[CH:25][C:4]=1[C:5]([N:7]1[CH2:11][CH2:10][C:9]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)([CH2:12][CH2:13]OS(C)(=O)=O)[CH2:8]1)=[O:6].I.[CH:35]([O:38][CH2:39][CH2:40][N:41]1[C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][C:44]=2[N:43]=[C:42]1[NH:50][CH:51]1[CH2:56][CH2:55][NH:54][CH2:53][CH2:52]1)([CH3:37])[CH3:36].C(N(CC)CC)C.ClCCl.CO>C(#N)C>[CH3:1][O:2][C:3]1[CH:28]=[CH:27][C:26]([N:29]2[CH:33]=[N:32][N:31]=[N:30]2)=[CH:25][C:4]=1[C:5]([N:7]1[CH2:11][CH2:10][C:9]([CH2:12][CH2:13][N:54]2[CH2:55][CH2:56][CH:51]([NH:50][C:42]3[N:41]([CH2:40][CH2:39][O:38][CH:35]([CH3:37])[CH3:36])[C:45]4[CH:46]=[CH:47][CH:48]=[CH:49][C:44]=4[N:43]=3)[CH2:52][CH2:53]2)([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH2:8]1)=[O:6]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 184648112-methoxy-5-(1H-tetrazol-1-yl)benzoyl-3-phenyl-3-(2-methanesulfonyloxyethyl)-pyrrolidineHCID 21226129Dichloromethane methanolHCID 86756598(1-(2-(Isopropoxy)ethyl)-1H-benzimidazol-2-yl)(piperidin-4-yl)amine hydriodic acid salt

Product 1

HCID 98746781-(2-methoxy-5-(1H-tetrazol-1-yl)benzoyl)-3-(2-(4-(1-(2-(isopropyloxy)ethyl)-1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-phenylpyrrolidine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

Combine 1-(2-methoxy-5-(1H-tetrazol-1-yl)benzoyl)-3-phenyl-3-(2-methanesulfonyloxyethyl)pyrrolidine (prepared from (−)-3-(2-hydroxyethyl)-3-phenylpyrrolidine (R,R)-di-p-anisoyltartaric acid salt) (0.52 g, 1.10 mmol), (1-(2-(isopropoxy)ethyl)-1H-benzimidazol-2-yl)(piperidin-4-yl)amine hydriodic acid salt (0.61 g, 1.09 mmol), and triethylamine (0.65 mL, 4.66 mmol) in acetonitrile (15 mL). Heat to 80° C. After 22 hours, evaporate in vacuo to give a residue. Partition the residue between dichloromethane and a saturated aqueous sodium bicarbonate solution. Separate the layers and extract the organic layer with water and then brine. Dry the organic layer over MgSO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting with dichloromethane/methanol/concentrated ammonium hydroxide, 95/5/0.05 to give the title compound: Rf=0.29 (silica gel, dichloromethane/methanol/concentrated ammonium hydroxide, 90/10/0.1).

Workup

  1. customevaporate in vacuo
  2. customto give a residue
  3. customPartition the residue between dichloromethane
  4. customSeparate the layers
  5. extractionextract the organic layer with water
  6. dry with materialDry the organic layer over MgSO4
  7. filtrationfilter
  8. customevaporate in vacuo
  9. customto give a residue

Sources & evidence

ORD record
ord-b7cdc415178148ecacc8e0194df0e2ae
Source dataset
uspto-grants-2001_04
Patent number
US06211199B1

Reaction notes

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