(1R,2S)-cyclobutane-1,2-diamine → rac-2-(3-((cis-2-aminocyclobutyl)amino)-2-methyl-5-quinoxalinyl)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one

HRID 1055885Notes

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.[C@@H:23]1([NH2:28])[CH2:26][CH2:25][C@@H:24]1[NH2:27]>CS(C)=O>[NH2:27][C@H:24]1[CH2:25][CH2:26][C@H:23]1[NH:28][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

Participants

Conditions

Temperature: 95 °C

Procedure

Prepared according to Example 127, using 2-(3-fluoro-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 126; 130 mg, 0.439 mmol), cis-cyclobutane-1,2-diamine (Frontier Scientific Services, Newark, Del.; 113 mg, 1.316 mmol), and DMSO (4.4 mL) and stirring at 95° C. for 2 h. Purification by reverse phase HPLC (Phenomenex Gemini column, 10 micron, C18, 100 Å, 150×30 mm, 0.1% TFA in ACN/H2O, gradient 5% to 70%) provided rac-2-(3-((cis-2-aminocyclobutyl)amino)-2-methyl-5-quinoxalinyl)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one (15 mg, 9.4%). 1H NMR (400 MHz, MeOH-d4) δ ppm 7.83-7.88 (1H, m) 7.55-7.61 (1H, m) 7.34 (1H, t, J=1.00 Hz) 7.09 (1H, s) 4.21-4.30 (1H, m) 3.59-3.67 (1H, m) 3.45-3.53 (1H, m) 3.16-3.23 (1H, m) 3.11-3.15 (1H, m) 2.93-3.08 (1H, m) 2.58 (3H, s) 2.34-2.42 (1H, m) 2.19-2.27 (1H, m) 1.56-1.69 (2H, m). m/z (ESI, +ve) 363.2 (M+H)+.

Workup

customPrepared
customPurification by reverse phase HPLC (Phenomenex Gemini column, 10 micron, C18, 100 Å, 150×30 mm, 0.1% TFA in ACN/H2O, gradient 5% to 70%)

Sources & evidence

ORD record: ord-518ab7b875b24847a530626adfc42f6d
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394297B2

Reaction notes

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