Cyclobutylamine → HCID 71731275, compound

HRID 1055958Notes

Reaction equation

HRID 1055958 reaction equation
F[C:2]1[C:3]([CH3:22])=[N:4][C:5]2[C:10]([N:11]=1)=[C:9]([C:12]1[NH:20][C:19]3[CH2:18][CH2:17][NH:16][C:15](=[O:21])[C:14]=3[CH:13]=1)[CH:8]=[CH:7][CH:6]=2.[CH:23]1([NH2:27])[CH2:26][CH2:25][CH2:24]1.CO.C(Cl)Cl>CS(C)=O.O>[CH:23]1([NH:27][C:2]2[C:3]([CH3:22])=[N:4][C:5]3[C:10]([N:11]=2)=[C:9]([C:12]2[NH:20][C:19]4[CH2:18][CH2:17][NH:16][C:15](=[O:21])[C:14]=4[CH:13]=2)[CH:8]=[CH:7][CH:6]=3)[CH2:26][CH2:25][CH2:24]1

Participants

6

Reactant 3

HCID 75645CyclobutylamineHCID 21226129Dichloromethane methanolHCID 897833202-(3-fluoro-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

Product 1

HCID 71731275HCID 71731275, compoundYield 64.5%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 2-(3-fluoro-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 126; 84.7 mg, 0.200 mmol) and cyclobutanamine (0.051 mL, 0.600 mmol) in DMSO (1.5 mL) was stirred under argon at 80° C. for 35 min. The mixture was cooled to 25° C. and diluted with water (40 mL). The resulting mixture was extracted with 5% MeOH/DCM (2×50 mL), and the combined extracts were sequentially washed with water (2×50 mL), dried over Na2SO4, filtered, and concentrated onto silica gel. Chromatographic purification (silica gel, 0-100% EtOAc/hexanes, then 0-10% MeOH/DCM) furnished 2-(3-(cyclobutylamino)-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (44.7 mg, 0.129 mmol, 64% yield) as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 12.37 (1H, br. s.), 7.90 (1H, dd, J=7.6, 1.2 Hz), 7.56 (1H, dd, J=8.0, 1.2 Hz), 7.39 (1H, d, J=6.3 Hz), 7.32 (1H, t, J=7.8 Hz), 7.10 (1H, d, J=2.0 Hz), 6.96 (1H, br. s.), 4.52 (1H, dq, J=15.2, 7.6 Hz), 3.45 (2H, td, J=6.8, 2.4 Hz), 2.92 (2H, t, J=6.8 Hz), 2.55 (3H, s), 2.42-2.48 (2H, m), 2.10-2.24 (2H, m), 1.78-1.91 (2H, m). m/z (ESI, +ve) 348.2 (M+H)+.

Workup

  1. extractionThe resulting mixture was extracted with 5% MeOH/DCM (2×50 mL)
  2. washthe combined extracts were sequentially washed with water (2×50 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated onto silica gel
  6. customChromatographic purification (silica gel, 0-100% EtOAc/hexanes

Sources & evidence

ORD record
ord-f1b316083edc490494ba11214738a3a1
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

Loading…