1-Hydroxybenzotriazole → 5-Phenyl-pyridine-2-carboxylic acid {2-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide

HRID 1093626노트

반응식

HRID 1093626 반응식
[C:1]1([C:7]2[CH:8]=[CH:9][C:10]([C:13]([NH:15][CH2:16][C:17]([OH:19])=O)=[O:14])=[N:11][CH:12]=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.[Cl:52][C:53]1[CH:65]=[CH:64][C:63]([F:66])=[CH:62][C:54]=1[O:55][CH:56]1[CH2:61][CH2:60][NH:59][CH2:58][CH2:57]1>CN(C=O)C.O>[Cl:52][C:53]1[CH:65]=[CH:64][C:63]([F:66])=[CH:62][C:54]=1[O:55][CH:56]1[CH2:57][CH2:58][N:59]([C:17](=[O:19])[CH2:16][NH:15][C:13]([C:10]2[CH:9]=[CH:8][C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)=[CH:12][N:11]=2)=[O:14])[CH2:60][CH2:61]1

참가 물질

8

반응물 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 167327404-(2-Chloro-5-fluoro-phenoxy)-piperidine hydrochlorideHCID 57874442[(5-Phenyl-pyridine-2-carbonyl)-amino]-acetic acid

생성물 1

HCID 442330225-Phenyl-pyridine-2-carboxylic acid {2-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide수율 54.6%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

To a stirred solution of [(5-phenyl-pyridine-2-carbonyl)-amino]-acetic acid (0.07 g, 0.00027 mol) in DMF (1.5 mL) was added DIPEA (0.105 g, 0.000819 mol), HOBt (0.044 g, 0.00033 mol) and EDCI.HCl (0.062 g, 0.00033 mol) at ambient temperature. After 2 minutes 4-(2-chloro-5-fluoro-phenoxy)-piperidine hydrochloride (0.087 g, 0.00033 mol) was and the resulting mixture was stirred overnight. The reaction mixture was then diluted with cold water and the product was extracted with ethyl acetate. The ethyl acetate layer was washed with brine solution, dried over sodium sulfate and concentrated under reduced pressure afford 0.069 g (54%) of 5-phenyl-pyridine-2-carboxylic acid {2-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LCMS: 468.14 (M+1)+, 82.99%, 1H NMR (DMSO-d6): δ 9.0 (d, 1H), 8.8 (t, 1H), 8.3 (dd, 1H), 8.1 (d, 1H), 7.8 (d, 2H), 7.6-7.4 (m, 4H), 7.2 (dd, 1H), 6.9-6.8 (m, 1H), 4.9-4.8 (m, 1H), 4.3 (d, 2H), 3.8-3.6 (m, 2H), 3.5 (m, 2H), 2.1-1.9 (m, 2H), 1.8-1.5 (m, 2H).

후처리

  1. extractionthe product was extracted with ethyl acetate
  2. washThe ethyl acetate layer was washed with brine solution
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-c20c3b041e874cf08061f84956da8e65
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08129376B2

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