Trifluoroacetic acid → HCID 58081326, compound

HRID 928432Notes

Reaction equation

HRID 928432 reaction equation
[CH3:1][C:2]1[C:7]([CH2:8][NH:9][C:10]([C:12]2[N:13]=[N:14][N:15]([CH2:17][C:18]3[CH:19]=[C:20]4[C:25](=[CH:26][CH:27]=3)[N:24]=[C:23]([CH3:28])[CH:22]=[CH:21]4)[CH:16]=2)=[O:11])=[C:6]([CH3:29])[N:5]=[C:4]([NH:30]C(=O)OC(C)(C)C)[CH:3]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:30][C:4]1[N:5]=[C:6]([CH3:29])[C:7]([CH2:8][NH:9][C:10]([C:12]2[N:13]=[N:14][N:15]([CH2:17][C:18]3[CH:19]=[C:20]4[C:25](=[CH:26][CH:27]=3)[N:24]=[C:23]([CH3:28])[CH:22]=[CH:21]4)[CH:16]=2)=[O:11])=[C:2]([CH3:1])[CH:3]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 58081212HCID 58081212, compound

Product 1

HCID 58081326HCID 58081326, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
23 °C

Procedure

To a solution of tert-butyl (4,6-dimethyl-5-((1-((2-methylquinolin-6-yl)methyl)-1H-1,2,3-triazole-4-carboxamido)methyl)pyridin-2-yl)carbamate (131.9 mg, 0.263 mmol) in DCM (1.2 ml) was added TFA (0.405 ml, 5.26 mmol). Reaction mixture was stirred overnight at 23° C. Reaction mixture was evaporated to afford the crude material, which was purified by preparative HPLC (Sunfire C18-ODB, 5 μm, 100×30 mm, elution with A=water+0.1% TFA and B=ACN+0.1% TFA, gradient from 5% to 100% B in 25 min, flow: 40 mL/min). Fractions were combined and acetonitrile was evaporated. Residual aqueous layer was frozen and lyophilized to afford the product as a TFA salt, which was dissolved in acetonitrile/methanol and eluted through a PL-HCO3 MP-resin column (Stratosphere SPE). The eluted solution was evaporated, and the residue was triturated in Et2O and filtered to afford the title compound as a free base. 1H-NMR (DMSO-d6, 400 MHz) δ 8.70 (s, 1H), 8.62 (broad s, 1H), 8.24 (d, 1H), 7.91 (d, 1H), 7.86 (s, 1H), 7.66 (d, 1H), 7.43 (d, 1H), 6.37 (broad s, 1H), 5.82 (s, 2H), 4.33 (d, 2H), 2.64 (s, 3H), 2.42 (s, 3H), 2.29 (s, 3H); HPLC (Method G) Rt=0.932 min; MS (Method F) [M+H]+=402.5.

Workup

  1. customReaction mixture
  2. customReaction mixture
  3. customwas evaporated
  4. customto afford the crude material, which
  5. customwas purified by preparative HPLC (
  6. washSunfire C18-ODB, 5 μm, 100×30 mm, elution with A=water+0.1% TFA and B=ACN+0.1% TFA, gradient from 5% to 100% B in 25 min
  7. customacetonitrile was evaporated
  8. temperatureResidual aqueous layer was frozen

Sources & evidence

ORD record
ord-12589cce2f8e43e299ff564a24991fa2
Source dataset
uspto-grants-2016_03
Patent number
US09290485B2

Reaction notes

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