Tert-Butylamine → HCID 118511961, compound

HRID 1055974Notes

Reaction equation

HRID 1055974 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.[CH3:24][C:25]([NH2:28])([CH3:27])[CH3:26].CO.C(Cl)Cl>CS(C)=O>[C:25]([NH:28][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)([CH3:27])([CH3:26])[CH3:24]

Participants

5

Reactant 3

HCID 6385Tert-ButylamineHCID 21226129Dichloromethane methanolHCID 89783714HCID 89783714, compound

Product 1

HCID 118511961HCID 118511961, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
100 °C

Procedure

2-(3-(tert-Butylamino)-2-methylquinoxalin-5-yl)-7-methyl-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one enantiomers were 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; 69.4 mg, 0.224 mmol) and 2-methylpropan-2-amine (TCI America, Portland, Oreg.; 0.071 mL, 0.671 mmol) in DMSO (1.0 mL), heating 100° C. for 1.5 h. Chromatographic purification (silica gel, 0-100% EtOAc/hexanes, then 0-10% MeOH/DCM) furnished rac-2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-7-methyl-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (43.6 mg, 0.120 mmol, 54% yield) as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 11.60 (1H, br. s.), 7.79 (1H, d, J=7.4 Hz), 7.59 (1H, d, J=8.2 Hz), 7.33 (1H, t, J=7.8 Hz), 6.95 (1H, s), 6.92 (1H, br. s.), 5.97 (1H, s), 3.45-3.55 (1H, m), 3.01-3.14 (2H, m), 2.55 (3H, s), 1.54 (9H, s), 1.27 (3H, d, J=6.3 Hz). m/z (ESI, +ve) 364.2 (M+H)+. Separation of this material by supercritical-fluid chromatography (Chiralpak AS-H (250×21 mm, 5 μm), 70% liquid CO2/30% MeOH (+20 mM NH3), 70 mL/min) separately afforded: 2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-7-methyl-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one, first-eluting enantiomer (162; 17.4 mg, 0.048 mmol) as a yellow solid; and 2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-7-methyl-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one, second-eluting enantiomer (163; 16.4 mg, 0.045 mmol) as a yellow solid.

Workup

  1. custom2-(3-(tert-Butylamino)-2-methylquinoxalin-5-yl)-7-methyl-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one enantiomers were prepared similar to
  2. customChromatographic purification (silica gel, 0-100% EtOAc/hexanes

Sources & evidence

ORD record
ord-978c47fa8980451e830dfe11ff4ebc71
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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