Sodium Bicarbonate → 1-(2-Methoxy-5-(1H-tetrazol-1-ylmethyl)benzoyl)-3-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepan-1-yl)ethyl)-3-phenylpyrrolidine

HRID 637143Notes

Reaction equation

HRID 637143 reaction equation
[CH2:1]([O:3][CH2:4][CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[N:8]=[C:7]1[N:15]1[CH2:21][CH2:20][CH2:19][N:18]([CH2:22][CH2:23][C:24]2([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH2:28][CH2:27][NH:26][CH2:25]2)[CH2:17][CH2:16]1)[CH3:2].C(=O)(O)[O-].[Na+].[CH3:40][O:41][C:42]1[CH:50]=[CH:49][C:48]([CH2:51][N:52]2[CH:56]=[N:55][N:54]=[N:53]2)=[CH:47][C:43]=1[C:44](Cl)=[O:45].CO.ClCCl>C(OCC)(=O)C.CCCCCC.CC(C)=O.C(OCC)(=O)C>[CH3:40][O:41][C:42]1[CH:50]=[CH:49][C:48]([CH2:51][N:52]2[CH:56]=[N:55][N:54]=[N:53]2)=[CH:47][C:43]=1[C:44]([N:26]1[CH2:27][CH2:28][C:24]([CH2:23][CH2:22][N:18]2[CH2:19][CH2:20][CH2:21][N:15]([C:7]3[N:6]([CH2:5][CH2:4][O:3][CH2:1][CH3:2])[C:10]4[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=4[N:8]=3)[CH2:16][CH2:17]2)([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:25]1)=[O:45]

Participants

8

Reactant 4

HCID 516892Sodium BicarbonateHCID 184646773-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepan-1-yl)ethyl)-3-phenylpyrrolidineHCID 184649562-Methoxy-5-(1H-tetrazol-1-ylmethyl)benzoyl ChlorideHCID 21226129Dichloromethane methanol

Product 1

HCID 184645101-(2-Methoxy-5-(1H-tetrazol-1-ylmethyl)benzoyl)-3-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepan-1-yl)ethyl)-3-phenylpyrrolidine

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 8857Ethyl AcetateSolvent2×HCID 21226206Ethyl acetate hexaneSolvent

Procedure

Combine 3-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepan-1-yl)ethyl)-3-phenylpyrrolidine (prepared from (−)-3-phenyl-3-(2-hydroxyethyl)pyrrolidine(R,R)-di-p-anisoyltartaric acid salt) (0.69 g, 1.49 mmol) and sodium bicarbonate (0.93 g, 11.07 mmol) in acetone/water (1/1, 40 mL). Cool in an ice bath. Add a solution of 2-methoxy-5-(1H-tetrazol-1-ylmethyl)benzoyl chloride (0.38 g, 1.49 mmol) in acetone (25 mL). After 18 hours, dilute the reaction mixture with ethyl acetate and extract twice with a saturated aqueous sodium bicarbonate solution and then brine. Dry the organic layer over Na2SO4, filter, and concentrate in vacuo to give a residue. Chromatograph the residue on silica gel eluting with ethyl acetate and then methanol/dichloromethane/concentrated aqueous ammonia 10/90/0.1 give the title compound: Rf=0.82 (silica gel, methanol/dichloromethane/concentrated aqueous ammonia 10/90/0.1).

Workup

  1. temperatureCool in an ice bath
  2. extractionextract twice with a saturated aqueous sodium bicarbonate solution
  3. dry with materialDry the organic layer over Na2SO4
  4. filtrationfilter
  5. concentrationconcentrate in vacuo
  6. customto give a residue

Sources & evidence

ORD record
ord-dc250308fb3e4acd830041a95ff2d6f0
Source dataset
uspto-grants-2001_02
Patent number
US06194406B1

Reaction notes

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