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

HRID 564365Notes

Reaction equation

HRID 564365 reaction equation
[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

Participants

10

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-6f4b2443db764713baa3af6380bd9c02
Source dataset
uspto-grants-2011_11
Patent number
US08067457B2

Reaction notes

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