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

HRID 564365ノート

反応式

HRID 564365 の反応式
[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

参加物

10

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-6f4b2443db764713baa3af6380bd9c02
出典データセット
uspto-grants-2011_11
特許番号
US08067457B2

反応ノート

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