1-Hydroxybenzotriazole → Biphenyl-4-carboxylic acid (2-{4-[(2-chloro-phenyl)-methyl-amino]-piperidin-1-yl}-2-oxo-ethyl)-amide

HRID 1093577노트

반응식

HRID 1093577 반응식
[C:1]1([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:6]=[CH:5][C:4]([C:7]([NH:9][CH2:10][C:11]([OH:13])=O)=[O:8])=[CH:3][CH:2]=1.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[Cl:52][C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=1[N:59]([CH3:66])[CH:60]1[CH2:65][CH2:64][NH:63][CH2:62][CH2:61]1>CN(C=O)C.O>[Cl:52][C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=1[N:59]([CH3:66])[CH:60]1[CH2:65][CH2:64][N:63]([C:11](=[O:13])[CH2:10][NH:9][C:7]([C:4]2[CH:3]=[CH:2][C:1]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[CH:6][CH:5]=2)=[O:8])[CH2:62][CH2:61]1

참가 물질

8

반응물 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2629432-((4-Phenylphenyl)formamido)acetic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66591723(2-Chloro-phenyl)-methyl-piperidin-4-yl-amine hydrochloride

생성물 1

HCID 44235273Biphenyl-4-carboxylic acid (2-{4-[(2-chloro-phenyl)-methyl-amino]-piperidin-1-yl}-2-oxo-ethyl)-amide수율 26.4%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

To a stirred solution of [(biphenyl-4-carbonyl)-amino]-acetic acid (0.0659 g, 0.00025 mol) in DMF (1 mL), was added DIPEA (0.0911 g, 0.0007 mol), HOBt (0.0318 g, 0.00023 mol) and EDCI.HCl (0.054 g, 0.00028 mol) at ambient temperature. After 2 minutes (2-chloro-phenyl)-methyl-piperidin-4-yl-amine hydrochloride (0.07 g, 0.00023 mol) was added and the resulting mixture was stirred at the same temperature overnight. The reaction mixture was diluted with cold water and the product was extracted with ethyl acetate. The ethyl acetate layer was washed with aqueous sodium bicarbonate solution followed by brine solution, dried over sodium sulfate and concentrated under reduced pressure. The resulting residue obtained was purified by column chromatography using basic aluminium oxide (10-30% ethyl acetate in hexane) to afford 0.028 g (23%) of biphenyl-4-carboxylic acid (2-{4-[(2-chloro-phenyl)-methyl-amino]-piperidin-1-yl}-2-oxo-ethyl)-amide. LCMS: 462.1 (M+1)+, 96.19%, 1H NMR (DMSO-d6): δ 8.6 (t, 1H), 7.95 (d, 2H), 7.75 (m, 3H), 7.5 (t, 2H), 7.42 (m, 2H), 7.3-7.2 (m, 2H), 7.05 (m, 1H), 4.4 (d, 1H), 4.2 (m, 2H), 3.95 (d, 1H), 3.05 (t, 1H), 2.65 (s, 3H), 1.6 (bs, 3H), 1.6-1.4 (m, 1H).

후처리

  1. extractionthe product was extracted with ethyl acetate
  2. washThe ethyl acetate layer was washed with aqueous sodium bicarbonate solution
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue obtained
  6. customwas purified by column chromatography

출처 및 근거

ORD 기록
ord-7f67f2db61754a3982ab24fad1dfc10f
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08129376B2

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