Trifluoroacetic acid → HCID 118512007, compound

HRID 1055947Notes

Reaction equation

HRID 1055947 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]([NH: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]([NH: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 89783981HCID 89783981, compound

Product 1

HCID 118512007HCID 118512007, compoundYield 38.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of (R)-tert-butyl 3-((8-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)quinolin-2-yl)amino)piperidine-1-carboxylate (78.0 mg, 0.169 mmol) and TFA (0.45 mL, 5.84 mmol) in DCM (1.5 mL) was stirred at 0° C. for 10 min, then at 25° C. for 1 h. The mixture was concentrated in vacuo, and the residue was taken up in DMSO (2.0 mL) and purified by reversed-phase HPLC (Phenomenex Gemini C18 column (150×30 mm, 10 μm), 35 mL/min, 5-100% ACN/H2O+0.1% TFA) to provide (R)-2-(2-(piperidin-3-ylamino)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one 2,2,2-trifluoroacetate (30.7 mg, 0.065 mmol, 38% yield) as a yellowish-brown solid: 1H NMR (400 MHz, MeOH-d4) δ ppm 8.08 (1H, dd, J=9.6, 4.1 Hz), 7.85 (1H, dd, J=7.5, 1.3 Hz), 7.65 (1H, d, J=7.4 Hz), 7.43 (1H, br. s.), 7.37 (1H, t, J=7.5 Hz), 6.96 (1H, d, J=7.2 Hz), 4.40-4.50 (1H, m), 3.79 (1H, dd, J=11.7, 2.3 Hz), 3.66 (2H, t, J=7.0 Hz), 3.43 (1H, dt, J=12.8, 4.3 Hz), 3.06-3.18 (2H, m), 3.03 (2H, t, J=7.1 Hz), 2.27-2.38 (1H, m), 2.10-2.22 (1H, m), 1.93-2.07 (1H, m), 1.72-1.85 (1H, m). 19F NMR (377 MHz, MeOH-d4) δ ppm −77.29 (3F, s). m/z (ESI, +ve) 362.1 (M+H)+.

Workup

  1. waitat 25° C. for 1 h
  2. concentrationThe mixture was concentrated in vacuo
  3. custompurified by reversed-phase HPLC (Phenomenex Gemini C18 column (150×30 mm, 10 μm), 35 mL/min, 5-100% ACN/H2O+0.1% TFA)

Sources & evidence

ORD record
ord-23cec40d61dc43068bb5f2bb1652ac17
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

Loading…