Trifluoroacetic acid → HCID 89783692, compound

HRID 1055909Notes

Reaction equation

HRID 1055909 reaction equation
[O:1]=[C:2]1[C:7]2[CH:8]=[C:9]([C:11]3[CH:12]=[CH:13][CH:14]=[C:15]4[C:20]=3[N:19]=[C:18]([O:21][CH:22]3[CH2:27][CH2:26][N:25](C(OC(C)(C)C)=O)[CH2:24][CH2:23]3)[CH:17]=[CH:16]4)[NH:10][C:6]=2[CH2:5][CH2:4][NH:3]1.[C:35]([OH:41])([C:37]([F:40])([F:39])[F:38])=[O:36]>C(Cl)Cl>[F:38][C:37]([F:40])([F:39])[C:35]([OH:41])=[O:36].[NH:25]1[CH2:24][CH2:23][CH:22]([O:21][C:18]2[CH:17]=[CH:16][C:15]3[C:20](=[C:11]([C:9]4[NH:10][C:6]5[CH2:5][CH2:4][NH:3][C:2](=[O:1])[C:7]=5[CH:8]=4)[CH:12]=[CH:13][CH:14]=3)[N:19]=2)[CH2:27][CH2:26]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 89793619HCID 89793619, compound

Product 1

HCID 89783692HCID 89783692, compoundYield 42.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of tert-butyl 4-((8-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)quinolin-2-yl)oxy)piperidine-1-carboxylate (0.103 g, 0.22 mmol) in DCM (3.0 mL) at 0° C. was added TFA (0.5 mL, 6.73 mmol). The reaction was stirred at 0° C. for 1 h, then at RT for 40 min. The reaction mixture was then concentrated, the residue was dissolved in DCM, washed with a saturated aq. solution of NaHCO3, dried over MgSO4, filtered and concentrated. The residue was dissolved in DMSO (2.0 mL) and purified by rpHPLC (Silicycle Silichrome XT C18 column; 30×150 mm, 5 μm, 5-95% 0.1% TFA/ACN in 0.1% TFA/water by volume over 10 min.), then dried in a Genevac Series II Evaporator to afford 2-(2-(piperidin-4-yloxy)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one 2,2,2-trifluoroacetate (48.7 mg, 0.094 mmol, 32.4% yield) as an amorphous orange solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 11.64 (br. s., 1H), 8.67 (br. s., 1H), 8.47 (br. s., 1H), 8.30 (d, J=9.0 Hz, 1H), 7.96 (d, J=7.2 Hz, 1H), 7.76 (d, J=8.2 Hz, 1H), 7.48 (t, J=7.8 Hz, 1H), 7.35 (d, J=2.0 Hz, 1H), 7.08 (d, J=8.8 Hz, 1H), 6.95 (br. s., 1H), 5.37-5.48 (m, 1H), 3.34-3.50 (m, 4H), 3.18-3.31 (m, 2H), 2.88 (t, J=6.8 Hz, 2H), 2.36 (d, J=14.3 Hz, 2H), 1.87-2.02 (m, 2H). 19F NMR (376 MHz, DMSO-d6) δ ppm −74.36 (s, 3F). m/z (ESI, +ve ion) 363.0 (M+H)+.

Workup

  1. waitat RT for 40 min
  2. concentrationThe reaction mixture was then concentrated
  3. dissolutionthe residue was dissolved in DCM
  4. washwashed with a saturated aq. solution of NaHCO3
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. dissolutionThe residue was dissolved in DMSO (2.0 mL)
  9. custompurified by rpHPLC (Silicycle Silichrome XT C18 column; 30×150 mm, 5 μm, 5-95% 0.1% TFA/ACN in 0.1% TFA/water by volume over 10 min.)
  10. dry with materialdried in a Genevac Series II Evaporator

Sources & evidence

ORD record
ord-d8f9b031b83c4069988131a3562f652a
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

Loading…