1,4'-Bipiperidine → (R)-3-(7-Methyl-1H-indazol-5-yl)-1-oxo-1-(4-(piperidin-1-yl)piperidin-1-yl)propan-2-yl 4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxylate

HRID 501956

Reaction equation

HRID 501956 reaction equation
[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: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](=[O:14])[N:54]3[CH2:55][CH2:56][CH:51]([N:45]4[CH2:50][CH2:49][CH2:48][CH2:47][CH2:46]4)[CH2:52][CH2:53]3)=[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

Participants

7

Reactant 4

HCID 786071,4'-BipiperidineHCID 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

Product 1

HCID 11685954(R)-3-(7-Methyl-1H-indazol-5-yl)-1-oxo-1-(4-(piperidin-1-yl)piperidin-1-yl)propan-2-yl 4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

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 (500 mg, 1.05 mmol), diisopropylethylamine (0.37 mL, 2.11 mmol), and 4-piperidinopiperidine (355 mg, 2.0 equiv) in dimethylformamide (4 mL) and dichloromethane (4 mL) at 0° C. was added PyBOP® (576 mg, 1.11 mmol). The reaction was stirred at 0° C. for 4 h, was concentrated, and purified by column chromatography (95:5:1 to 93:7:1 dichloromethane/methanol/triethylamine). The resulting residue was dissolved in 5% methanol/dichloromethane and passed through a basic alumina column to give 600 mg (88%) as a white powder. Mass spec.: 625.56 (MH)+.

Workup

  1. concentrationwas concentrated
  2. custompurified by column chromatography (95:5:1 to 93:7:1 dichloromethane/methanol/triethylamine)
  3. dissolutionThe resulting residue was dissolved in 5% methanol/dichloromethane
  4. customto give 600 mg (88%) as a white powder

Sources & evidence

ORD record
ord-0055b98dd3d247bbb00da879f4195822
Source dataset
uspto-grants-2010_08
Patent number
US07772244B2

Linked notes

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