Cyclopropylamine → HCID 71731149, compound

HRID 1055972Notes

Reaction equation

HRID 1055972 reaction equation
F[C:2]1[C:3]([CH3:23])=[N:4][C:5]2[C:10]([N:11]=1)=[C:9]([C:12]1[NH:20][C:19]3[CH:18]([CH3:21])[CH2:17][NH:16][C:15](=[O:22])[C:14]=3[CH:13]=1)[CH:8]=[CH:7][CH:6]=2.[CH:24]1([NH2:27])[CH2:26][CH2:25]1.CO.C(Cl)Cl>CS(C)=O>[CH:24]1([NH:27][C:2]2[C:3]([CH3:23])=[N:4][C:5]3[C:10]([N:11]=2)=[C:9]([C:12]2[NH:20][C:19]4[CH:18]([CH3:21])[CH2:17][NH:16][C:15](=[O:22])[C:14]=4[CH:13]=2)[CH:8]=[CH:7][CH:6]=3)[CH2:26][CH2:25]1

Participants

5

Reactant 3

HCID 69828CyclopropylamineHCID 21226129Dichloromethane methanolHCID 89783714HCID 89783714, compound

Product 1

HCID 71731149HCID 71731149, compoundYield 84.1%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
100 °C

Procedure

Prepared similar to that described in Example 131 using rac-2-(3-fluoro-2-methylquinoxalin-5-yl)-7-methyl-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 156; 62.4 mg, 0.201 mmol) and cyclopropanamine (Alfa Aesar, Ward Hill, Mass.; 0.042 mL, 0.603 mmol) in DMSO (1.0 mL), heating at 100° C. for 1.5 h. Chromatographic purification (silica gel, 0-100% EtOAc/hexanes, then 0-10% MeOH/DCM) furnished rac-2-(3-(cyclopropylamino)-2-methylquinoxalin-5-yl)-7-methyl-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (58.8 mg, 0.169 mmol, 84% yield) as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 12.51 (1H, br. s.), 7.99 (1H, d, J=7.4 Hz), 7.53-7.64 (2H, m), 7.36 (1H, t, J=7.7 Hz), 7.18 (1H, d, J=1.8 Hz), 6.98 (1H, br. s.), 3.46-3.58 (1H, m), 3.05-3.20 (2H, m), 2.88-2.98 (1H, m), 2.51 (3H, br. s.), 1.24 (3H, d, J=6.5 Hz), 0.88-1.00 (2H, m), 0.68-0.78 (2H, m). m/z (ESI, +ve) 348.2 (M+H)+. Separation of this material by supercritical-fluid chromatography (Chiralpak AS-H (250×21 mm, 5 μn), 60% liquid CO2/40% MeOH (+20 mM NH3), 70 mL/min) separately afforded: 2-(3-(cyclopropylamino)-2-methylquinoxalin-5-yl)-7-methyl-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one, first-eluting enantiomer (160; 19.6 mg, 0.056 mmol) as a yellow solid; and 2-(3-(cyclopropylamino)-2-methylquinoxalin-5-yl)-7-methyl-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one, second-eluting enantiomer (161; 19.2 mg, 0.055 mmol) as a yellow solid.

Workup

  1. customPrepared similar to
  2. customChromatographic purification (silica gel, 0-100% EtOAc/hexanes

Sources & evidence

ORD record
ord-475a8dd606f74b1082288d19e50f776c
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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