1-(4-Pyridyl)piperazine → (R)-3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-(4-(pyridin-4-yl)piperazin-1-yl)propan-2-yl 4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxylate

HRID 501965

반응식

HRID 501965 반응식
[CH3:1][C:2]1[CH:3]=[C:4]([CH2:11][C@@H:12]([O:16][C:17]([N:19]2[CH2:24][CH2:23][CH:22]([C:25]3[C:26](=[O:35])[NH:27][C:28]4[C:33]([CH:34]=3)=[CH:32][CH:31]=[CH:30][CH:29]=4)[CH2:21][CH2:20]2)=[O:18])[C:13](O)=[O:14])[CH:5]=[C:6]2[C:10]=1[NH:9][N:8]=[CH:7]2.C(N(C(C)C)CC)(C)C.[N:45]1[CH:50]=[CH:49][C:48]([N:51]2[CH2:56][CH2:55][NH:54][CH2:53][CH2:52]2)=[CH:47][CH:46]=1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C)C=O.ClCCl>[O:35]=[C:26]1[C:25]([CH:22]2[CH2:21][CH2:20][N:19]([C:17]([O:16][C@H:12]([CH2:11][C:4]3[CH:5]=[C:6]4[C:10](=[C:2]([CH3:1])[CH:3]=3)[NH:9][N:8]=[CH:7]4)[C:13](=[O:14])[N:54]3[CH2:55][CH2:56][N:51]([C:48]4[CH:49]=[CH:50][N:45]=[CH:46][CH:47]=4)[CH2:52][CH2:53]3)=[O:18])[CH2:24][CH2:23]2)=[CH:34][C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[NH:27]1

참가 물질

7

반응물 4

HCID 705171-(4-Pyridyl)piperazineHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 59424312(R)-3-(7-Methyl-1H-indazol-5-yl)-2-(4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carbonyloxy)propanoic acid

생성물 1

HCID 11512851(R)-3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-(4-(pyridin-4-yl)piperazin-1-yl)propan-2-yl 4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxylate

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

반응 조건

온도
0 °C

실험 절차

To a solution of (R)-3-(7-methyl-1H-indazol-5-yl)-2-(4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carbonyloxy)propanoic acid (50 mg, 0.11 mmol), diisopropylethylamine (37 μL, 0.21 mmol), and 1-(4-pyridyl)piperazine (34.4 mg, 2.0 equiv) in dimethylformamide (0.50 mL) and dichloromethane (0.50 mL) at 0° C. was added PyBOP® (57.6 mg, 0.11 mmol). The reaction was stirred at 0° C. for 4 h, was concentrated, and purified by column chromatography (95:5:1 to 90:10:1 dichloromethane/methanol/triethylamine). The resulting residue was dissolved in 5% methanol/dichloromethane and passed through a basic alumina column to give 53.8 mg (80%) as a white powder. 1H-NMR (CD3OD, 500 MHz) δ 1.25-2.00 (m, 4H), 2.51 (s, 3H), 2.67 (bs, 1H), 2.80-3.31 (m, 7H), 3.35-3.83 (m, 5H), 4.05-4.49 (m, 2H), 5.52 (dd, J=7.6, 7.3, 1H), 6.64 (bs, 2H), 7.12 (s, 11H), 7.22 (dd, J=7.0, 7.0, 1H), 7.32 (d, J=8.2, 1H), 7.47 (m, 1H), 7.52 (m, 1.5H), 7.62 (d, J=7.0, 11H), 7.69 (bs, 0.5H), 7.99 (s, 1H), 8.10 (m, 2H). Mass spec.: 620.28 (MH)+.

후처리

  1. concentrationwas concentrated
  2. custompurified by column chromatography (95:5:1 to 90:10:1 dichloromethane/methanol/triethylamine)
  3. dissolutionThe resulting residue was dissolved in 5% methanol/dichloromethane
  4. customto give 53.8 mg (80%) as a white powder

출처 및 근거

ORD 기록
ord-4e9fe93fa8a24bf787f95dc7e3d875f3
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07772244B2

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