1-Hydroxybenzotriazole → 5-Phenyl-isoxazole-3-carboxylic acid (2-{4-[(2-bromo-phenyl)-methyl-amino]-piperidin-1-yl}-2-oxo-ethyl)-amide

HRID 1093586노트

반응식

HRID 1093586 반응식
[C:1]1([C:7]2[O:11][N:10]=[C:9]([C:12]([NH:14][CH2:15][C:16]([OH:18])=O)=[O:13])[CH:8]=2)[CH:6]=[CH:5][CH:4]=[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.[Br:51][C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][C:53]=1[N:58]([CH3:65])[CH:59]1[CH2:64][CH2:63][NH:62][CH2:61][CH2:60]1>CN(C=O)C.O>[Br:51][C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][C:53]=1[N:58]([CH3:65])[CH:59]1[CH2:64][CH2:63][N:62]([C:16](=[O:18])[CH2:15][NH:14][C:12]([C:9]2[CH:8]=[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[O:11][N:10]=2)=[O:13])[CH2:61][CH2:60]1

참가 물질

8

반응물 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 433543392-[(5-Phenyl-1,2-oxazol-3-yl)formamido]acetic acidHCID 66591780HCID 66591780, 화합물

생성물 1

HCID 442355035-Phenyl-isoxazole-3-carboxylic acid (2-{4-[(2-bromo-phenyl)-methyl-amino]-piperidin-1-yl}-2-oxo-ethyl)-amide수율 35%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

To a stirred solution of [(5-phenyl-isoxazole-3-carbonyl)-amino]-acetic acid (62.9 mg, 0.00025 mol) in DMF (2 mL) was added DIPEA (0.159 g, 0.00123 mol), HOBt (41.4 mg, 0.00031 mol) and EDCI.HCl (58.8 mg, 0.0003° mol) at ambient temperature. After 2 minutes (2-bromo-phenyl)-methyl-piperidin-4-yl-amine hydrochloride (0.068 g, 0.00025 mol) was added and the resulting mixture was stirred overnight. The reaction mixture was then diluted with cold water and the resulting precipitate was isolated by filtration. Purification by column chromatography using basic aluminium oxide (50-100% ethyl acetate in hexane) afforded 0.039 g (35%) of 5-phenyl-isoxazole-3-carboxylic acid (2-{4-[(2-bromo-phenyl)-methyl-amino]-piperidin-1-yl}-2-oxo-ethyl)-amide. LCMS: 497.11 (M+1)+, 97.87%, 1H NMR (DMSO-d6): δ 8.58 (t, 1H), 7.93 (m, 2H), 7.52 (m, 4H), 7.4 (s, 1H), 7.15 (m, 2H), 6.9 (m, 1H), 4.3 (d, 1H), 4.15 (t, 2H), 3.8 (d, 1H), 3.0 (m, 1H), 2.65 (m, 1H), 2.55 (s, 3H), 1.75 (m, 3H), 1.5 (m, 2H).

후처리

  1. customthe resulting precipitate was isolated by filtration
  2. customPurification by column chromatography

출처 및 근거

ORD 기록
ord-03baa656b5604f45907c48a782ec07dc
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08129376B2

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