Trifluoroacetic acid → HCID 118511965, compound

HRID 1055914Notes

Reaction equation

HRID 1055914 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][C@H:22]3[CH2:27][CH2:26][CH2:25][N:24](C(OC(C)(C)C)=O)[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:24]1[CH2:25][CH2:26][CH2:27][C@H: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)[CH2:23]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 89783551HCID 89783551, compound

Product 1

HCID 118511965HCID 118511965, compoundYield 22.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (S)-tert-butyl 3-((8-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)quinolin-2-yl)oxy)piperidine-1-carboxylate (117 mg, 0.25 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 20 min then at RT for 2 h. The solution was concentrated, the residue was dissolved in DCM and washed with a saturated aq. solution of NaHCO3. The organic layer was separated, and the aq. layer was extracted with DCM (2×). The combined organic layers were then concentrated, and the residue was dissolved in DMSO (3 mL). Purification by rpHPLC (Silicycle Silichrome XT C18 column; 30×150 mm, 5 m, 5-95% 0.1% TFA/ACN in 0.1% TFA/water by volume over 10 min.), then drying in a Genevac Series II Evaporator afforded (S)-2-(2-(piperidin-3-yloxy)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one 2,2,2-trifluoroacetate (27.3 mg, 0.057 mmol, 22.7% yield) as an amorphous brown solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 11.62 (br. s., 1H), 8.69-8.85 (m, 2H), 8.33 (d, J=8.8 Hz, 1H), 7.95 (d, J=7.4 Hz, 1H), 7.78 (d, J=7.8 Hz, 1H), 7.49 (t, J=7.7 Hz, 1H), 7.16 (d, J=2.0 Hz, 1H), 7.09 (d, J=8.8 Hz, 1H), 7.02 (br. s., 1H), 5.51 (br. s., 1H), 3.40-3.53 (m, 4H), 3.14 (br. s., 2H), 2.89 (t, J=6.8 Hz, 2H), 2.11-2.23 (m, 1H), 1.94-2.05 (m, 2H), 1.81-1.90 (m, 1H). 19F NMR (376 MHz, DMSO-d6) δ ppm −74.35 (s, 3F). m/z (ESI, +ve ion) 363.0 (M+H)+.

Workup

  1. waitat RT for 2 h
  2. concentrationThe solution was concentrated
  3. dissolutionthe residue was dissolved in DCM
  4. washwashed with a saturated aq. solution of NaHCO3
  5. customThe organic layer was separated
  6. extractionthe aq. layer was extracted with DCM (2×)
  7. concentrationThe combined organic layers were then concentrated
  8. dissolutionthe residue was dissolved in DMSO (3 mL)
  9. customPurification by rpHPLC (Silicycle Silichrome XT C18 column; 30×150 mm, 5 m, 5-95% 0.1% TFA/ACN in 0.1% TFA/water by volume over 10 min.)
  10. dry with materialdrying in a Genevac Series II Evaporator

Sources & evidence

ORD record
ord-1cb4843aece3473bb97c88ec281c7932
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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