Trifluoroacetic acid → N-((6-amino-2,4-dimethylpyridin-3-yl)methyl)-1-((7-chloroquinolin-2-yl)methyl)-1H-pyrazole-4-carboxamide

HRID 928439Notes

Reaction equation

HRID 928439 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([CH2:12][N:13]3[CH:17]=[C:16]([C:18]([NH:20][CH2:21][C:22]4[C:23]([CH3:37])=[CH:24][C:25]([NH:29]C(=O)OC(C)(C)C)=[N:26][C:27]=4[CH3:28])=[O:19])[CH:15]=[N:14]3)=[N:9]2)=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:29][C:25]1[N:26]=[C:27]([CH3:28])[C:22]([CH2:21][NH:20][C:18]([C:16]2[CH:15]=[N:14][N:13]([CH2:12][C:8]3[CH:7]=[CH:6][C:5]4[C:10](=[CH:11][C:2]([Cl:1])=[CH:3][CH:4]=4)[N:9]=3)[CH:17]=2)=[O:19])=[C:23]([CH3:37])[CH:24]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 58081351tert-butyl (5-((1-((7-chloroquinolin-2-yl)methyl)-1H-pyrazole-4-carboxamido)methyl)-4,6-dimethylpyridin-2-yl)carbamate

Product 1

HCID 58081168N-((6-amino-2,4-dimethylpyridin-3-yl)methyl)-1-((7-chloroquinolin-2-yl)methyl)-1H-pyrazole-4-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
23 °C

Procedure

To a solution of tert-butyl (5-((1-((7-chloroquinolin-2-yl)methyl)-1H-pyrazole-4-carboxamido)methyl)-4,6-dimethylpyridin-2-yl)carbamate (151 mg, 0.29 mmol) in DCM (2 ml) was added TFA (0.447 ml, 5.80 mmol). Reaction mixture was stirred for 7.5 h at 23° C. After evaporation of solvents, the crude material 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 the solvents were evaporated to afford the title cpd as a TFA salt, which was dissolved in hot methanol/ACN and eluted through a PL-HCO3 MP-resin column (Stratosphere SPE) in order to remove salt. The eluted solution was evaporated, and the residue was dried over a weekend under high vacuum (dessicator, 50° C.) to afford the title compound as a free base. 1H-NMR (DMSO-d6, 400 MHz) δ 8.40 (d, 1H), 8.38 (s, 1H), 8.03 (s, 1H), 8.02 (d, 1H), 7.94 (broad s, 2H), 7.65 (d, 1H), 7.24 (d, 1H), 6.11 (s, 1H), 5.63 (s, 2H), 5.61 (broad s, 2H), 4.28 (d, 2H), 2.29 (s, 3H), 2.16 (s, 3H); HPLC (Method G) Rt=1.476 min, MS (Method V) [M+H]+=422.3.

Workup

  1. customReaction mixture
  2. customAfter evaporation of solvents
  3. customthe crude material was purified by preparative HPLC (
  4. 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
  5. customthe solvents were evaporated

Sources & evidence

ORD record
ord-00735859cbf14a658a8234c8920c4034
Source dataset
uspto-grants-2016_03
Patent number
US09290485B2

Reaction notes

Loading…