1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-[(3R)-1-benzylpyrrolidin-3-yl]-2-[4-(trifluoromethyl)-1H-benzimidazol-2-yl]acetamide

HRID 564365Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 564365
[Li].[F:2][C:3]([F:18])([F:17])[C:4]1[C:12]2[N:11]=[C:10]([CH2:13][C:14]([OH:16])=O)[NH:9][C:8]=2[CH:7]=[CH:6][CH:5]=1.[CH2:19]([N:26]1[CH2:30][CH2:29][C@@H:28]([NH2:31])[CH2:27]1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.C(N(C(C)C)CC)(C)C.C([O-])(O)=O.[Na+]>CN(C=O)C.ClCCl>[CH2:19]([N:26]1[CH2:30][CH2:29][C@@H:28]([NH:31][C:14](=[O:16])[CH2:13][C:10]2[NH:9][C:8]3[CH:7]=[CH:6][CH:5]=[C:4]([C:3]([F:2])([F:18])[F:17])[C:12]=3[N:11]=2)[CH2:27]1)[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Komponenten

10

Edukt 7

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 1519354(3R)-1-benzylpyrrolidin-3-amineHCID 3028194LithiumHCID 21111780(4-trifluoromethyl-1H-benzoimidazol-2-yl)-acetic acid

Produkt 1

HCID 67004693N-[(3R)-1-benzylpyrrolidin-3-yl]-2-[4-(trifluoromethyl)-1H-benzimidazol-2-yl]acetamideAusbeute 62 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of the lithium salt of [4-(trifluoromethyl)-1H-benzimidazol-2-yl]acetic acid (3.5 mmol; prepared according to WO 2005020899 A2) in DMF (18 mL) was added (3R)-1-benzylpyrrolidin-3-amine (740 mg, 4.20 mmol), HOBt (709 mg, 5.25 mmol), EDCI (1.00 g, 5.25 mmol) and diisopropylethylamine (3.05 mL, 17.5 mmol). The reaction mixture was stirred for 16 hours then was added NaHCO3 (sat. aq., 10 mL) and dichloromethane (10 mL). The organic layer was separated and the aqueous layer was washed with an addition portion of dichloromethane (10 mL). The organic layers were combined, dried over Na2SO4, filtered and concentrated. The resulting crude product was subjected to flash chromatography (15% MeOH, 1% NH4OH in EtOAc) to afford N-[(3R)-1-benzylpyrrolidin-3-yl]-2-[4-(trifluoromethyl)-1H-benzimidazol-2-yl]acetamide (866 mg, 62%) as a white solid.

Aufarbeitung

  1. customThe organic layer was separated
  2. washthe aqueous layer was washed with an addition portion of dichloromethane (10 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-6f4b2443db764713baa3af6380bd9c02
Quelldatensatz
uspto-grants-2011_11
Patentnummer
US08067457B2

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