Trifluoroacetic acid → HCID 71730505, compound

HRID 1056217Notes

Reaction equation

HRID 1056217 reaction equation
[CH3:1][C:2]([NH:13][C:14]1[C:23]([CH3:24])=[N:22][C:21]2[C:16](=[C:17]([C:25]3[NH:33][C:32]4[CH2:31][CH2:30][NH:29][C:28](=[O:34])[C:27]=4[CH:26]=3)[CH:18]=[CH:19][CH:20]=2)[N:15]=1)([CH3:12])[CH2:3][NH:4]C(=O)OC(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:4][CH2:3][C:2]([NH:13][C:14]1[C:23]([CH3:24])=[N:22][C:21]2[C:16]([N:15]=1)=[C:17]([C:25]1[NH:33][C:32]3[CH2:31][CH2:30][NH:29][C:28](=[O:34])[C:27]=3[CH:26]=1)[CH:18]=[CH:19][CH:20]=2)([CH3:12])[CH3:1]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71730371HCID 71730371, compound

Product 1

HCID 71730505HCID 71730505, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of tert-butyl (2-methyl-2-((3-methyl-8-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)quinoxalin-2-yl)amino)propyl)carbamate (339) (0.13 g, 0.28 mmol) in DCM (2.80 mL) and TFA (1.0 mL, 13.99 mmol) was stirred at 0° C. for 20 min before it was warmed to RT and stir for 1 h. The reaction mixture was concentrated and the residue was diluted with CHCl3/IPA(3:2) (150 mL), added to a separatory funnel, and washed with saturated aq. NaHCO3 (2×75 mL) before the organic layer was separated, dried over Na2SO4, and concentrated to give 2-(3-((1-amino-2-methylpropan-2-yl)amino)-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (65 mg, 0.17 mmol, 63% yield) which was impure by NMR. This material was dissolved in MeOH (˜20 mg/mL) and injected (2×1.0 mL) onto the Shimadzu preparatory LC (Phenomenex Gemini C18, 10 μm, 150×30 mm; 10-100% MeCN/water with 0.1% TFA); the pure fractions were combined, basicified with NaHCO3 (saturated, aq.), extracted with CHCl3/IPA(3:2), separated, dried over Na2SO4, and concentrated via rotary evaporation to give 2-(3-((1-amino-2-methylpropan-2-yl)amino)-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (341) (19 mg, 0.05 mmol, 18% yield) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ ppm 1.60 (s, 6H) 2.59 (s, 3H) 2.95 (s, 2H) 2.99 (t, J=6.85 Hz, 2H) 3.65 (td, J=6.85, 2.54 Hz, 2H) 5.33 (br. s., 1H) 6.19 (s, 1H) 7.10 (d, J=2.15 Hz, 1H) 7.36 (t, J=7.82 Hz, 1H) 7.65 (dd, J=8.02, 1.37 Hz, 1H) 7.92 (dd, J=7.63, 1.37 Hz, 1H) 12.64 (br. s., 1H). MS (ESI, pos. ion) m/z: 365.3 (M+1).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additionthe residue was diluted with CHCl3/IPA(3:2) (150 mL)
  3. additionadded to a separatory funnel
  4. washwashed with saturated aq. NaHCO3 (2×75 mL) before the organic layer
  5. customwas separated
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-0f6a99f56e0748c4be6af0627f727150
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

Loading…