Trifluoroacetic acid → HCID 58081222, compound

HRID 928436Notes

Reaction equation

HRID 928436 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]=[N:20][C:21]4[C:26]([CH:27]=3)=[CH:25][CH:24]=[C:23]([CH3:28])[CH:22]=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.CO>[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]=[N:20][C:21]4[C:26]([CH:27]=3)=[CH:25][CH:24]=[C:23]([CH3:28])[CH:22]=4)[CH:16]=2)=[O:11])=[C:2]([CH3:1])[CH:3]=1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 58081353HCID 58081353, compound

Product 1

HCID 58081222HCID 58081222, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
23 °C

Procedure

To a solution of tert-butyl (4,6-dimethyl-5-((1-((7-methylquinolin-3-yl)methyl)-1H-1,2,3-triazole-4-carboxamido)methyl)pyridin-2-yl)carbamate (70 mg, 0.140 mmol) in DCM (1 ml) was added TFA (0.215 ml, 2.79 mmol). Reaction mixture was stirred over a weekend at 23° C. Reaction mixture was evaporated to afford a crude product, which was purified by preparative HPLC (Sunfire C18-ODB, 5 μm, 100×30 mm, elution with A=water+0.1% HCOOH and B=ACN+0.1% HCOOH, gradient from 10% to 100% B in 25 min, flow: 40 mL/min). Fractions were combined and solvents were evaporated to afford athe product as a formic acid salt, which was dissolved in methanol and eluted through a PL-HCO3 MP-resin column (Stratosphere SPE) in order to remove salt. The eluted solution was evaporated and dried overnight under high vacuum (dessicator, 50° C.) to afford the title compound as a free base. 1H-NMR (DMSO-d6, 400 MHz) δ 8.90 (s, 1H), 8.72 (s, 1H), 8.30 (broad s, 1H), 8.26 (s, 1H), 7.89 (d, 1H), 7.83 (s, 1H), 7.49 (d, 1H), 6.10 (s, 1H), 5.87 (s, 2H), 5.61 (broad s, 2H), 4.33 (d, 2H), 2.54 (s, 3H), 2.31 (s, 3H), 2.18 (s, 3H); HPLC (Method G) Rt=1.079 min; MS (Method V) [M+H]+=402.4.

Workup

  1. customReaction mixture
  2. customReaction mixture
  3. customwas evaporated
  4. customto afford a crude product, which
  5. customwas purified by preparative HPLC (
  6. washSunfire C18-ODB, 5 μm, 100×30 mm, elution with A=water+0.1% HCOOH and B=ACN+0.1% HCOOH, gradient from 10% to 100% B in 25 min
  7. customsolvents were evaporated
  8. customto afford athe product as a formic acid salt, which
  9. washeluted through a PL-HCO3 MP-resin column (Stratosphere SPE) in order
  10. customto remove salt
  11. customThe eluted solution was evaporated
  12. customdried overnight under high vacuum (dessicator, 50° C.)

Sources & evidence

ORD record
ord-11d61b923265417499fe63c4568f577b
Source dataset
uspto-grants-2016_03
Patent number
US09290485B2

Reaction notes

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