Diisopropylethylamine → 1-(2-Methylthio-5-(1H-tetrazol-1-yl)benzoyl)-3-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepan-1-yl)ethyl)-3-phenylpyrrolidine

HRID 637112Notes

Reaction equation

HRID 637112 reaction equation
Cl.[CH2:2]([O:4][CH2:5][CH2:6][N:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[N:9]=[C:8]1[N:16]1[CH2:22][CH2:21][CH2:20][N:19]([CH2:23][CH2:24][C:25]2([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH2:29][CH2:28][NH:27][CH2:26]2)[CH2:18][CH2:17]1)[CH3:3].[CH3:36][S:37][C:38]1[CH:46]=[CH:45][C:44]([N:47]2[CH:51]=[N:50][N:49]=[N:48]2)=[CH:43][C:39]=1[C:40](O)=[O:41].O.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.Cl.C(N=C=NCCCN(C)C)C>C(OCC)(=O)C.ClCCl.CO.C(OCC)(=O)C>[CH3:36][S:37][C:38]1[CH:46]=[CH:45][C:44]([N:47]2[CH:51]=[N:50][N:49]=[N:48]2)=[CH:43][C:39]=1[C:40]([N:27]1[CH2:28][CH2:29][C:25]([CH2:24][CH2:23][N:19]2[CH2:20][CH2:21][CH2:22][N:16]([C:8]3[N:7]([CH2:6][CH2:5][O:4][CH2:2][CH3:3])[C:11]4[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=4[N:9]=3)[CH2:17][CH2:18]2)([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH2:26]1)=[O:41]

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 184645182-Methylthio-5-(1H-tetrazol-1-yl)benzoic AcidHCID 184649573-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepan-1-yl)ethyl)-3-phenylpyrrolidine hydrochloric acid

Product 1

HCID 184646101-(2-Methylthio-5-(1H-tetrazol-1-yl)benzoyl)-3-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepan-1-yl)ethyl)-3-phenylpyrrolidine

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent2×HCID 21584119Ethylacetate methanolSolvent2×

Procedure

Combine 3-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepan-1-yl)ethyl)-3-phenylpyrrolidine hydrochloric acid salt (prepared from (−)-3-phenyl-3-(2-hydroxyethyl)pyrrolidine(R,R)-di-p-anisoyltartaric acid salt) (0.53 g, 1.0 mmol) and dichloromethane (10 mL). Add 2-methylthio-5-(1H-tetrazol-1-yl)benzoic acid (0.24 g, 1.0 mmol), 1-hydroxybenzotriazole hydrate (0.16 g, 1.2 mmol), N,N-diisopropylethylamine (0.34 mL, 2.0 mmol), and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.23 g, 1.2 mmol). After 18 hours, dilute the reaction mixture with ethyl acetate and extract with brine. Dry the organic layer over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting sequentially with ethyl acetate, 2% methanol/ethyl acetate, and the 8% methanol/ethyl acetate to give a residue. Combine the residue and dichloromethane, extract with brine, twice with a saturated aqueous solution of ammonium chloride, and then a saturated aqueous solution of sodium bicarbonate. Dry the organic layer over MgSO4, filter, and evaporate in vacuo to give the title compound: Rf=0.34 (silica gel, 10% methanol/ethyl acetate).

Workup

  1. extractionextract with brine
  2. dry with materialDry the organic layer over Na2SO4
  3. filtrationfilter
  4. customevaporate in vacuo
  5. customto give a residue
  6. extractionextract with brine, twice with a saturated aqueous solution of ammonium chloride
  7. dry with materialDry the organic layer over MgSO4
  8. filtrationfilter
  9. customevaporate in vacuo

Sources & evidence

ORD record
ord-4083b7c96d5f486ebf04c1785cb7df22
Source dataset
uspto-grants-2001_02
Patent number
US06194406B1

Reaction notes

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