Trifluoroacetic acid → HCID 67959696, compound

HRID 1529403Notes

Reaction equation

HRID 1529403 reaction equation
[C:1]([OH:7])([C:3]([F:6])([F:5])[F:4])=[O:2].[CH3:8][C:9]1([C:12]2[CH:13]=[C:14]3[C:18](=[CH:19][CH:20]=2)[N:17](C2CCCCO2)[N:16]=[C:15]3[C:27]2[N:32]=[C:31]([O:33][C@H:34]3[CH2:41][N:40](C(OC(C)(C)C)=O)[CH2:39][CH2:38][C:35]43[CH2:37][CH2:36]4)[CH:30]=[N:29][CH:28]=2)[CH2:11][CH2:10]1>C(Cl)Cl>[F:4][C:3]([F:6])([F:5])[C:1]([OH:7])=[O:2].[CH2:37]1[C:35]2([CH2:38][CH2:39][NH:40][CH2:41][C@@H:34]2[O:33][C:31]2[N:32]=[C:27]([C:15]3[C:14]4[C:18](=[CH:19][CH:20]=[C:12]([C:9]5([CH3:8])[CH2:11][CH2:10]5)[CH:13]=4)[NH:17][N:16]=3)[CH:28]=[N:29][CH:30]=2)[CH2:36]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67960025HCID 67960025, compound

Product 1

HCID 67959696HCID 67959696, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

TFA (1.7 mL, 22.07 mmol) was added to a solution of (4R)-tert-butyl 4-(6-(5-(1-methylcyclopropyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yloxy)-6-azaspiro[2.5]octane-6-carboxylate (96.3 mg, 0.172 mmol) in DCM (1.7 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-methylcyclopropyl)-1H-indazole 2,2,2-trifluoroacetate (64.6 mg, 0.132 mmol, 77% yield) as a yellow solid: 1H NMR (400 MHz, MeOH) δ ppm 9.02 (1 H, s), 8.26-8.33 (1H, m), 8.17-8.22 (1 H, m), 7.54 (1 H, d, J=8.8 Hz), 7.43 (1 H, dd, J=8.7, 1.5 Hz), 5.09 (1H, s), 3.90 (1 H, d, J=13.1 Hz), 3.60 (1 H, d, J=12.3 Hz), 3.47-3.55 (1 H, m), 3.33-3.39 (1 H, m), 2.65-2.77 (1 H, m), 1.49 (3 H, s), 1.23 (1 H, d, J=14.7 Hz), 1.01 (1 H, dt, J=9.7, 5.1 Hz), 0.90-0.95 (2 H, m), 0.82-0.90 (3 H, m), 0.75-0.81 (1 H, m), 0.64-0.73 (1 H, m). 19F NMR (377 MHz, MeOH) δ ppm −77.48 (3 F, s). MS (ESI, pos. ion) m/z: 376.3 (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-8e74a0cbece94bf1a9a9d33eb745f6bb
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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