(R)-3-(7-Methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-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 → (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 501947Notes

Reaction equation

HRID 501947 reaction equation
[O:1]=[C:2]1[C:11]([CH:12]2[CH2:17][CH2:16][N:15]([C:18]([O:20][C@H:21]([CH2:36][C:37]3[CH:45]=[C:44]([CH3:46])[C:43]4[C:39](=[CH:40][N:41](COCC[Si](C)(C)C)[N:42]=4)[CH:38]=3)[C:22](=[O:35])[N:23]3[CH2:28][CH2:27][CH:26]([N:29]4[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]4)[CH2:25][CH2:24]3)=[O:19])[CH2:14][CH2:13]2)=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[NH:3]1>FC(F)(F)C(O)=O>[O:1]=[C:2]1[C:11]([CH:12]2[CH2:13][CH2:14][N:15]([C:18]([O:20][C@H:21]([CH2:36][C:37]3[CH:38]=[C:39]4[C:43](=[C:44]([CH3:46])[CH:45]=3)[NH:42][N:41]=[CH:40]4)[C:22](=[O:35])[N:23]3[CH2:24][CH2:25][CH:26]([N:29]4[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34]4)[CH2:27][CH2:28]3)=[O:19])[CH2:16][CH2:17]2)=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[NH:3]1

Participants

3

Reactant 1

HCID 59424305(R)-3-(7-Methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-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

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 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

(R)-3-(7-Methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-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 (102 mg, 0.14 mmol) was dissolved in trifluoroacetic acid (50% in dichloromethane, 6 mL), and stirred at room temperature for 2 h. The reaction was concentrated and purified by column chromatography (5:95:1 methanol/dichloromethane/triethylamine). The residue was dissolved in 10% methanol/dichloromethane and passed through a plug of basic alumina to give 56.4 mg (67%) as a white solid. 1H-NMR (CD3OD, 500 MHz) δ −0.50-0.01 (m, 0.7H), 0.50-0.85 (m, 0.8H), 1.00-2.05 (m, 16H), 2.05-2.55 (m, 7H), 2.55-3.00 (m, 4H), 3.00-3.15 (m, 2H), 3.70-4.50 (m, 4H), 5.41 (m, 0.3H), 5.48 (dd, J=9.5, 6.1, 0.6H), 7.01 (m, 1H), 7.11 (m, 1H), 7.21 (m, 1H), 7.36 (m, 2H), 7.44-7.65 (m, 2H), 7.90 (m, 1H). Mass spec.: 625.33 (MH)+.

Workup

  1. concentrationThe reaction was concentrated
  2. custompurified by column chromatography (5:95:1 methanol/dichloromethane/triethylamine)
  3. dissolutionThe residue was dissolved in 10% methanol/dichloromethane
  4. customto give 56.4 mg (67%) as a white solid

Sources & evidence

ORD record
ord-33c89710767243b89ef29d8479275bbe
Source dataset
uspto-grants-2010_08
Patent number
US07772244B2

Reaction notes

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