Trifluoroacetic acid → HCID 86709785, compound

HRID 1529400Notes

Reaction equation

HRID 1529400 reaction equation
[C:1]([OH:7])([C:3]([F:6])([F:5])[F:4])=[O:2].O1CCCCC1[N:14]1[C:22]2[C:17](=[CH:18][C:19]([C:23]3([C:26]([F:29])([F:28])[F:27])[CH2:25][CH2:24]3)=[CH:20][CH:21]=2)[C:16]([C:30]2[N:35]=[C:34]([O:36][C@H:37]3[CH2:44][N:43](C(OC(C)(C)C)=O)[CH2:42][CH2:41][C:38]43[CH2:40][CH2:39]4)[CH:33]=[N:32][CH:31]=2)=[N:15]1>C(Cl)Cl>[F:4][C:3]([F:6])([F:5])[C:1]([OH:7])=[O:2].[F:4][C:3]([F:6])([F:5])[C:1]([OH:7])=[O:2].[F:4][C:3]([F:6])([F:5])[C:1]([OH:7])=[O:2].[CH2:39]1[C:38]2([CH2:41][CH2:42][NH:43][CH2:44][C@@H:37]2[O:36][C:34]2[N:35]=[C:30]([C:16]3[C:17]4[C:22](=[CH:21][CH:20]=[C:19]([C:23]5([C:26]([F:27])([F:28])[F:29])[CH2:25][CH2:24]5)[CH:18]=4)[NH:14][N:15]=3)[CH:31]=[N:32][CH:33]=2)[CH2:40]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86709786HCID 86709786, compound

Product 1

HCID 86709785HCID 86709785, compoundYield 39%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

TFA (0.5 mL, 6.49 mmol) was added to a solution of (4R)-tert-butyl 4-((6-(1-(tetrahydro-2H-pyran-2-yl)-5-(1-(trifluoromethyl)cyclopropyl)-1H-indazol-3-yl)pyrazin-2-yl)oxy)-6-azaspiro[2.5]octane-6-carboxylate (25.2 mg, 0.041 mmol) in DCM (0.5 mL) and the resulting solution was stirred at 25° C. for 2 h. The mixture was concentrated in vacuo and the residue was taken up in DMSO (2.0 mL) and purified by rpHPLC (Phenomenex Gemini C18 column (150×30 mm, 10 μm), 35 mL/min, 5-100% CH3CN/H2O+0.1% TFA, 15 min, 254 nm) to provide 3-(6-((4R)-6-azaspiro[2.5]oct-4-yloxy)-2-pyrazinyl)-5-(1-(trifluoromethyl)cyclopropyl)-1H-indazole tris(2,2,2-trifluoroacetate) (12.0 mg, 0.016 mmol, 38% yield) as a yellow foam: 1H NMR (400 MHz, MeOH-d4) δ ppm 9.04 (1 H, s), 8.42-8.46 (1 H, m), 8.31 (1 H, s), 7.60-7.64 (1 H, m), 7.55-7.59 (1 H, m), 5.07 (1 H, s), 3.89 (1 H, d, J=12.7 Hz), 3.57 (1 H, m, J=13.3, 1.0 Hz), 3.47-3.54 (1 H, m), 3.34-3.39 (1 H, m), 2.72 (1 H, td, J=13.9, 4.5 Hz), 1.45-1.49 (2 H, m), 1.22-1.27 (1 H, m), 1.17-1.22 (2 H, m), 0.99 (1 H, dt, J=8.9, 5.6 Hz), 0.77-0.85 (2 H, m), 0.67-0.73 (1 H, m). 19F NMR (377 MHz, MeOH) δ ppm −71.41 (3 F, s), −77.45 (9 F, br. s.). MS (ESI, pos. ion) m/z: 430.1 (M+1).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. custompurified by rpHPLC (Phenomenex Gemini C18 column (150×30 mm, 10 μm), 35 mL/min, 5-100% CH3CN/H2O+0.1% TFA, 15 min, 254 nm)

Sources & evidence

ORD record
ord-d1c9dd4ff15c4c65af74d9d67cf3c6f8
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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