Diisopropylethylamine → (R)-1-(4-cyclohexylpiperazin-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 501963

Reaktionsgleichung

Reaktionsgleichung von HRID 501963
[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.[CH:45]1([N:51]2[CH2:56][CH2:55][NH:54][CH2:53][CH2:52]2)[CH2:50][CH2:49][CH2:48][CH2:47][CH2:46]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[CH2:23][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:54]3[CH2:55][CH2:56][N:51]([CH:45]4[CH2:50][CH2:49][CH2:48][CH2:47][CH2:46]4)[CH2:52][CH2:53]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

Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 872981-CyclohexylpiperazineHCID 2724699PyBOPHCID 59424312(R)-3-(7-Methyl-1H-indazol-5-yl)-2-(4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carbonyloxy)propanoic acid

Produkt 1

HCID 11498219(R)-1-(4-cyclohexylpiperazin-1-yl)-3-(7-methyl-1H-indazol-5-yl)-1-oxopropan-2-yl 4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

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-cyclohexylpiperazine (35.5 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% methanol/dichloromethane and passed through a basic alumina column to give 62.3 mg (92%) as a white powder. 1H-NMR (CD3OD, 500 MHz) δ 0.75-2.10 (m, 20H), 2.29 (m, 1H), 2.47 (m, 1H), 2.56 (s, 3H), 2.77-3.41 (m, 9H), 3.73 (m, 1H), 4.04-4.49 (m, 2H), 5.52 (dd, J=8.2, 7.3, 1H), 7.11 (s, 1H), 7.22 (dd, J=7.0, 7.0, 1H), 7.33 (d, J=7.9, 1H), 7.42-7.53 (m, 2H), 7.53-7.76 (m, 2H), 8.01 (s, 1H). Mass spec.: 625.33 (MH)+.

Aufarbeitung

  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% methanol/dichloromethane
  4. customto give 62.3 mg (92%) as a white powder

Quellen und Nachweise

ORD-Eintrag
ord-5a345e4c0f084d588531ece5ed53f756
Quelldatensatz
uspto-grants-2010_08
Patentnummer
US07772244B2

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