Trifluoroacetic acid → N-[3-[5-amino-6-(6-methyl-1H-benzimidazol-2-yl)pyrazin-2-yl]prop-2-ynyl]methanesulfonamide

HRID 1853141Notes

Reaction equation

HRID 1853141 reaction equation
[NH2:1][CH2:2][C:3]#[C:4][C:5]1[N:10]=[C:9]([C:11]2[N:15](C(OC(C)(C)C)=O)[C:14]3[CH:23]=[C:24]([CH3:27])[CH:25]=[CH:26][C:13]=3[N:12]=2)[C:8]([N:28](C(OC(C)(C)C)=O)C(OC(C)(C)C)=O)=[N:7][CH:6]=1.CCN(CC)CC.[S:50](Cl)([CH3:53])(=[O:52])=[O:51].C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:28][C:8]1[N:7]=[CH:6][C:5]([C:4]#[C:3][CH2:2][NH:1][S:50]([CH3:53])(=[O:52])=[O:51])=[N:10][C:9]=1[C:11]1[NH:15][C:14]2[CH:23]=[C:24]([CH3:27])[CH:25]=[CH:26][C:13]=2[N:12]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 86661949HCID 86661949, compound

Product 1

HCID 54597013N-[3-[5-amino-6-(6-methyl-1H-benzimidazol-2-yl)pyrazin-2-yl]prop-2-ynyl]methanesulfonamideYield 4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

tert-Butyl 2-[6-(3-aminoprop-1-ynyl)-3-(bis(tert-butoxycarbonyl)amino)pyrazin-2-yl]-6-methyl-benzimidazole-1-carboxylate (90 mg, 0.1555 mmol) and Et3N (23.60 mg, 32.51 μL, 0.2332 mmol) were dissolved in DCM (10 mL) and cooled to 0° C. in and ice bath. Mesyl chloride (21.38 mg, 14.45 μL, 0.1866 mmol) as a solution in DCM (1 mL) was added dropwise and the reaction stirred at 0° C. for 20 minutes. The reaction mixture was washed with saturated aqueous NaHCO3 (×1) and brine (×1), dried (MgSO4), filtered and concentrated in vacuo. The residue was redissolved in DCM (10 mL) and TFA (177.3 mg, 119.8 μL, 1.555 mmol) added. The reaction mixture was stirred at ambient temperature for 1 hour then concentrated in vacuo. The residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 mM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. The fractions were collected and freeze-dried to give the title compound as an yellow solid (2 mg, 4% Yield). 1H NMR (400.0 MHz, D4-MeOH) δ 1.6 (3H, s), 2.25 (3H, s), 3.25 (2H, s), 6.25 (1H, d), 6.55 (1H, s), 6.7 (1H, d), 7.3 (1H, s); MS (ES+) 357.

Workup

  1. washThe reaction mixture was washed with saturated aqueous NaHCO3 (×1) and brine (×1)
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was redissolved in DCM (10 mL)
  6. stirringThe reaction mixture was stirred at ambient temperature for 1 hour
  7. concentrationthen concentrated in vacuo
  8. customThe residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 mM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]
  9. customThe fractions were collected
  10. customfreeze-dried

Sources & evidence

ORD record
ord-eca3677dd5a54da882ee380bd50fada5
Source dataset
uspto-grants-2015_02
Patent number
US08962631B2

Reaction notes

Loading…