Diisopropylethylamine → rac-2-(2-methyl-3-((tetrahydro-2H-pyran-3-yl)amino)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

HRID 1056017Notes

Reaction equation

HRID 1056017 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.Cl.[O:24]1[CH2:29][CH2:28][CH2:27][CH:26]([NH2:30])[CH2:25]1.CCN(C(C)C)C(C)C>>[CH3:22][C:3]1[C:2]([NH:30][CH:26]2[CH2:27][CH2:28][CH2:29][O:24][CH2:25]2)=[N:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[C:12]2[NH:20][C:19]3[CH2:18][CH2:17][NH:16][C:15](=[O:21])[C:14]=3[CH:13]=2)[N:4]=1

Participants

4

Reactant 3

HCID 81531DiisopropylethylamineHCID 46735995Oxan-3-amine hydrochlorideHCID 897833202-(3-fluoro-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

Product 1

HCID 89783738rac-2-(2-methyl-3-((tetrahydro-2H-pyran-3-yl)amino)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-oneYield 75%

Conditions

Temperature
100 °C

Procedure

Prepared similarly to that described in Example 131 using 2-(3-fluoro-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 126; 44 mg, 0.148 mmol), rac-tetrahydro-2H-pyran-3-amine hydrochloride (40.9 mg, 0.297 mmol, Matrix Scientific, Columbia, S.C.), and DIPEA (129 μl, 0.742 mmol), heating at 100° C. for 1 h. Purification by silica gel (100% DCM to 6% MeOH/DCM) provided rac-2-(2-methyl-3-((tetrahydro-2H-pyran-3-yl)amino)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (75% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.72-1.83 (m, 3H) 2.13-2.21 (m, 1H) 2.56 (s, 3H) 2.91 (t, J=6.85 Hz, 2H) 3.35-3.42 (m, 2H) 3.45 (td, J=6.85, 2.35 Hz, 2H) 3.87 (d, J=10.76 Hz, 1H) 4.01-4.08 (m, 1H) 4.12-4.20 (m, 1H) 6.86 (d, J=7.24 Hz, 1H) 6.94 (br. s., 1H) 7.08 (d, J=2.15 Hz, 1H) 7.35 (t, J=7.82 Hz, 1H) 7.59 (dd, J=8.12, 1.27 Hz, 1H) 7.91 (dd, J=7.53, 1.27 Hz, 1H) 12.07 (br. s., 1H). MS (ESI, pos. ion) m/z: 378.2 (M+1). Chiral purification [SFC: Chiralpak OH-J (30×150 mm), A: liquid CO2, B: 20 mM NH3 in MeOH/EtOH/isopropanol (1:1:1), isocratic: 70:30 (A:B), 70 mL/min] separately afforded 2-(2-methyl-3-((tetrahydro-2H-pyran-3-yl)amino)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (first eluting enantiomer, 208) and 2-(2-methyl-3-((tetrahydro-2H-pyran-3-yl)amino)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (second eluting enantiomer, 209).

Workup

  1. customPrepared similarly to that
  2. customPurification by silica gel (100% DCM to 6% MeOH/DCM)

Sources & evidence

ORD record
ord-aeb8ede8fb9d414aa36ca1b5ebec0035
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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