Trifluoroacetic acid → (S)-4-(1-acetyl-2-methyl-6-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-1,2,3,4-tetrahydroquinolin-5-yloxy)benzamide

HRID 1051625Notes

Reaction equation

HRID 1051625 reaction equation
FC(F)(F)C(O)=O.[C:8]([N:11]1[C:20]2[C:15](=[C:16]([O:39][C:40]3[CH:45]=[CH:44][C:43]([C:46](=[O:48])[NH2:47])=[CH:42][CH:41]=3)[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[CH3:49])(=[O:10])[CH3:9]>ClCCl>[C:8]([N:11]1[C:20]2[C:15](=[C:16]([O:39][C:40]3[CH:41]=[CH:42][C:43]([C:46]([NH2:47])=[O:48])=[CH:44][CH:45]=3)[C:17]([C:21]3[CH:22]=[N:23][N:24]([CH:26]4[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]4)[CH:25]=3)=[CH:18][CH:19]=2)[CH2:14][CH2:13][C@@H:12]1[CH3:49])(=[O:10])[CH3:9]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 118075594HCID 118075594, compound

Product 1

HCID 118075880(S)-4-(1-acetyl-2-methyl-6-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-1,2,3,4-tetrahydroquinolin-5-yloxy)benzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (3.5 mL) was added to a solution of tert-butyl 4-[4-[(2S)-1-acetyl-5-(4-carbamoylphenoxy)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl]-1H-pyrazol-1-yl]piperidine-1-carboxylate (0.080 g, 0.14 mmol) in dichloromethane (30 mL). The reaction mixture stirred for 2 h at room temperature and was then concentrated under vacuum. The residue was dissolved in dichloromethane (50 mL), washed with saturated aqueous potassium carbonate solution (3×20 mL) and brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was purified by preparative-HPLC with the following conditions (Prep-HPLC-12): Column, XBridge Prep C18 OBD Column, 19×150 mm 5 um 13 nm; mobile phase: water (0.05% ammonium bicarbonate) and acetonitrile (20% to 95% acetonitrile in 18 min, flow rate: 20 mL/min); Detector, UV 254/220 nm. This afforded 4-[[(2S)-1-acetyl-2-methyl-6-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]-1,2,3,4-tetrahydroquinolin-5-yl]oxy]benzamide (0.033 g, 50%) as an off-white solid.

Workup

  1. concentrationwas then concentrated under vacuum
  2. dissolutionThe residue was dissolved in dichloromethane (50 mL)
  3. washwashed with saturated aqueous potassium carbonate solution (3×20 mL) and brine (20 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by preparative-HPLC with the following conditions (Prep-HPLC-12)
  8. customwater (0.05% ammonium bicarbonate) and acetonitrile (20% to 95% acetonitrile in 18 min, flow rate: 20 mL/min)

Sources & evidence

ORD record
ord-c590103e188b4e829e6ec5a6c677523f
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

Loading…