Trifluoroacetic acid → (S)-1-(2-methyl-6-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-5-propoxy-3,4-dihydroquinolin-1(2H)-yl)ethanone

HRID 1051605Notes

Reaction equation

HRID 1051605 reaction equation
FC(F)(F)C(O)=O.[C:8]([N:11]1[C:20]2[C:15](=[C:16]([O:39][CH2:40][CH2:41][CH3:42])[C:17]([C:21]3[CH:22]=[N:23][N:24]([CH:26]4[CH2:31][CH2:30][N:29](C(OC(C)(C)C)=O)[CH2:28][CH2:27]4)[CH:25]=3)=[CH:18][CH:19]=2)[CH2:14][CH2:13][C@@H:12]1[CH3:43])(=[O:10])[CH3:9]>ClCCl>[CH3:43][C@H:12]1[CH2:13][CH2:14][C:15]2[C:20](=[CH:19][CH:18]=[C:17]([C:21]3[CH:22]=[N:23][N:24]([CH:26]4[CH2:27][CH2:28][NH:29][CH2:30][CH2:31]4)[CH:25]=3)[C:16]=2[O:39][CH2:40][CH2:41][CH3:42])[N:11]1[C:8](=[O:10])[CH3:9]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 118076049(5)-tert-butyl 4-(4-(1-acetyl-2-methyl-5-propoxy-1,2,3,4-tetrahydroquinolin-6-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate

Product 1

HCID 118075413(S)-1-(2-methyl-6-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-5-propoxy-3,4-dihydroquinolin-1(2H)-yl)ethanoneYield 89.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (0.5 mL, 6.49 mmol) was added to a solution of (S)-tert-butyl 4-(4-(1-acetyl-2-methyl-5-propoxy-1,2,3,4-tetrahydroquinolin-6-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (0.063 g, 0.127 mmol) in dichloromethane (2.0 mL) and the reaction mixture stirred at rt for 1.5 h. The reaction mixture was concentrated and the residue was partitioned between dichloromethane and saturated aqueous sodium bicarbonate solution. The organic phase was separated, dried over anhydrous sodium sulfate, filtered, and concentrated to afford (S)-1-(2-methyl-6-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-5-propoxy-3,4-dihydroquinolin-1(2H)-yl)ethanone (0.045 g, 89%) as a tan solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.91-1.12 (m, 6H), 1.18-1.37 (m, 1H), 1.57-1.88 (m, 5H), 1.97 (br d, J=10.26 Hz, 2H), 2.07 (s, 3H), 2.16-2.40 (m, 2H), 2.53-2.66 (m, 2H), 2.73-2.89 (m, 1H), 3.03 (br d, J=12.61 Hz, 2H), 3.46-3.65 (m, 2H), 4.09-4.30 (m, 1H), 4.62 (br d, J=5.86 Hz, 1H), 7.11 (br d, J=8.21 Hz, 1H), 7.38 (d, J=8.21 Hz, 1H), 7.84 (s, 1H), 8.09 (s, 1H). MS (ESI, pos. ion) m/z 397 [M+H]+.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customthe residue was partitioned between dichloromethane and saturated aqueous sodium bicarbonate solution
  3. customThe organic phase was separated
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-cec22a69f2fd4bb199e5be600347d3f8
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

Loading…