Trifluoroacetic acid → (S)-cyclopropyl(5-(2,6-dimethylpyridin-4-yloxy)-2-methyl-6-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-3,4-dihydroquinolin-1(2H)-yl)methanone

HRID 1051712Notes

Reaction equation

HRID 1051712 reaction equation
FC(F)(F)C(O)=O.[CH:8]1([C:11]([N:13]2[C:22]3[C:17](=[C:18]([O:41][C:42]4[CH:47]=[C:46]([CH3:48])[N:45]=[C:44]([CH3:49])[CH:43]=4)[C:19]([C:23]4[CH:24]=[N:25][N:26]([CH:28]5[CH2:33][CH2:32][N:31](C(OC(C)(C)C)=O)[CH2:30][CH2:29]5)[CH:27]=4)=[CH:20][CH:21]=3)[CH2:16][CH2:15][C@@H:14]2[CH3:50])=[O:12])[CH2:10][CH2:9]1>ClCCl>[CH:8]1([C:11]([N:13]2[C:22]3[C:17](=[C:18]([O:41][C:42]4[CH:43]=[C:44]([CH3:49])[N:45]=[C:46]([CH3:48])[CH:47]=4)[C:19]([C:23]4[CH:24]=[N:25][N:26]([CH:28]5[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]5)[CH:27]=4)=[CH:20][CH:21]=3)[CH2:16][CH2:15][C@@H:14]2[CH3:50])=[O:12])[CH2:9][CH2:10]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 118076088(S)-tert-butyl 4-(4-(1-(cyclopropanecarbonyl)-5-(2, 6-dimethylpyridin-4-yloxy)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate

Product 1

HCID 118075962(S)-cyclopropyl(5-(2,6-dimethylpyridin-4-yloxy)-2-methyl-6-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-3,4-dihydroquinolin-1(2H)-yl)methanone

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (1 mL) was added to a solution of (S)-tert-butyl 4-(4-(1-(cyclopropanecarbonyl)-5-(2,6-dimethylpyridin-4-yloxy)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (0.030 g, 0.05 mmol) in dichloromethane (3 mL), and the resulting solution stirred for 1 h at room temperature. The reaction mixture was concentrated under vacuum, and the residue was purified via column chromatography on silica gel (eluting with 1:2, ethyl acetate/petroleum ether). The crude product was further purified by preparative-HPLC with the following conditions (Waters I): Column, SunFire Prep C18, 5 um, 19×100 mm; mobile phase, water (0.05% ammonium bicarbonate) and acetonitrile (65% to 85% acetonitrile in 7 min, flow rate: 20 mL/min); Detector, UV 220254 nm. This afforded (S)-cyclopropyl(5-(2,6-dimethylpyridin-4-yloxy)-2-methyl-6-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-3,4-dihydroquinolin-1(2H)-yl)methanone (0.003 g, 12%) as a white powder. 1H NMR (400 MHz, CD3OD) δ ppm 0.73-0.84 (m, 1H), 0.92-1.03 (m, 2H), 1.12-1.21 (m, 4H), 1.42-1.51 (m, 1H), 1.99-2.20 (m, 5H), 2.20-2.29 (m, 2H), 2.29-2.41 (m, 6H), 2.63-2.72 (m, 1H), 2.95-3.04 (m, 2H), 3.31-3.41 (m, 2H), 4.35-4.45 (m, 1H), 4.79-4.90 (m, 1H), 6.53 (s, 2H), 7.45 (d, J=8.40 Hz, 1H), 7.63 (d, J=8.80 Hz, 1H), 7.79 (s, 1H), 7.96 (s, 1H). MS (ESI, pos. ion) m/z 486 [M+H]+.

Workup

  1. concentrationThe reaction mixture was concentrated under vacuum
  2. customthe residue was purified via column chromatography on silica gel (eluting with 1:2, ethyl acetate/petroleum ether)
  3. customThe crude product was further purified by preparative-HPLC with the following conditions (Waters I)
  4. custommobile phase, water (0.05% ammonium bicarbonate) and acetonitrile (65% to 85% acetonitrile in 7 min, flow rate: 20 mL/min)

Sources & evidence

ORD record
ord-e0ab3db1face432eaf3df9b07878f872
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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