1-(4-Fluorophenyl)piperazine → (R)-1-(4-(4-fluorophenyl)piperazin-1-yl)-3-(7-methyl-1H-indazol-5-yl)-1-oxopropan-2-yl 4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxylate

HRID 501964

반응식

HRID 501964 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.[F:45][C:46]1[CH:51]=[CH:50][C:49]([N:52]2[CH2:57][CH2:56][NH:55][CH2:54][CH2:53]2)=[CH:48][CH:47]=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[CH2:23][CH2:24][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]([N:55]3[CH2:54][CH2:53][N:52]([C:49]4[CH:48]=[CH:47][C:46]([F:45])=[CH:51][CH:50]=4)[CH2:57][CH2:56]3)=[O:14])=[O:18])[CH2:20][CH2:21]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 752601-(4-Fluorophenyl)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 11599872(R)-1-(4-(4-fluorophenyl)piperazin-1-yl)-3-(7-methyl-1H-indazol-5-yl)-1-oxopropan-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 N-(4-fluorophenyl)piperazine (38.0 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. The reaction was concentrated and purified by column chromatography (95:5:1 to 90:10:1 dichloromethane/methanol/triethylamine). The resulting residue was dissolved in 5% methanoudichloromethane and passed through a basic alumina column to give 71.2 mg (quant.) as a white powder. 1H-NMR (CD3OD, 500 MHz) δ 1.25-1.75 (m, 2H), 1.75-2.25 (m, 9H), 2.51 (s, 3H), 2.75 (m, 1H), 2.75-3.30 (m, 13H), 3.48 (m, 3H), 3.80 (m, 1H), 4.05-4.50 (m, 2H), 5.55 (dd, J=7.6, 7.3, 1H), 6.68 (m, 2H), 6.91 (m, 1H), 7.11 (s, 1H), 7.21 (dd, J=7.9, 7.3, 1H), 7.32 (d, J=8.2, 1H), 7.47 (dd, J=7.9, 7.3, 1H), 7.51 (m, 1.5H), 7.61 (d, J=7.6, 1H), 7.67 (bs, 0.5H), 8.00 (s, 1H). Mass spec.: 637.28 (MH)+.

후처리

  1. concentrationThe reaction was concentrated
  2. custompurified by column chromatography (95:5:1 to 90:10:1 dichloromethane/methanol/triethylamine)
  3. dissolutionThe resulting residue was dissolved in 5% methanoudichloromethane
  4. customto give 71.2 mg (quant.) as a white powder

출처 및 근거

ORD 기록
ord-1521ad7e0bf346659ee2923b2c267d84
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07772244B2

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