HCID 89793640, compound → HCID 89784271, compound

HRID 1055943Notes

Reaction equation

HRID 1055943 reaction equation
[NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][C@H:4]([NH:8][C:9]2[CH:18]=[CH:17][C:16]3[C:11](=[C:12]([C:19]4[NH:27][C:26]5[CH2:25][CH2:24][NH:23][C:22](=[O:28])[C:21]=5[CH:20]=4)[CH:13]=[CH:14][CH:15]=3)[N:10]=2)[CH2:3]1>C(=O)=O.C(NCC)C.N1C=CC=CC=1C(N)=O>[NH2:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][C@H:4]([NH:8][C:9]2[CH:18]=[CH:17][C:16]3[C:11](=[C:12]([C:19]4[NH:27][C:26]5[CH2:25][CH2:24][NH:23][C:22](=[O:28])[C:21]=5[CH:20]=4)[CH:13]=[CH:14][CH:15]=3)[N:10]=2)[CH2:3]1

Participants

5

Reactant 1

HCID 89793640HCID 89793640, compound

Product 1

HCID 89784271HCID 89784271, compound

Reagents, catalysts & solvents 3

HCID 280Carbon DioxideSolvent2×HCID 8021DiethylamineSolvent2×HCID 150702-PyridinecarboxamideSolvent

Procedure

A solution of 2-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 1; 101 mg, 0.339 mmol) and cyclohexane-1,3-diamine (Aldich; 0.204 mL, 1.696 mmol) in DMSO (0.6 mL) was stirred under argon at 100° C. for 1 d. The mixture was cooled to 25° C., diluted with DMSO (1.8 mL), and purified by revered-phase HPLC (Phenomenex Gemini C18 column (150×30 mm, 10 μm), 35 mL/min, 5-100% ACN/H2O+0.1% TFA) to provide 2-(2-((3-aminocyclohexyl)amino)-quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one 2,2,2-trifluoroacetate (159.8 mg, 0.326 mmol, 96% yield) as a yellow-brown solid: m/z (ESI, +ve) 376.3 (M+H)+. Separation of this material by supercritical-fluid chromatography (Chiralcel OD-H (150×21 mm, 5 μm), 60% liquid CO2/40% MeOH (+0.2% diethylamine), 75 mL/min, followed by repurification of 122 by Princeton Chromatography pyridine amide column (250×21 mm, 5 μm), 70% liquid CO2/30% MeOH (+0.2% diethylamine), 75 mL/min) separately afforded rac-2-(2-((trans-3-aminocyclohexyl)amino)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (120; 4.5 mg, 0.012 mmol) as a light-yellow solid: 1H NMR (400 MHz, MeOH-d4) δ ppm 7.94 (1H, dd, J=7.5, 1.1 Hz), 7.84 (1H, d, J=9.0 Hz), 7.46 (1H, dd, J=7.7, 0.9 Hz), 7.20 (1H, t, J=7.6 Hz), 7.03 (1H, s), 6.87 (1H, d, J=9.0 Hz), 4.39 (1H, br. s.), 3.62 (2H, t, J=7.0 Hz), 3.14 (1H, t, J=9.9 Hz), 3.02 (2H, td, J=7.0, 2.6 Hz), 2.34 (1H, d, J=13.7 Hz), 1.89-2.01 (2H, m), 1.74-1.85 (3H, m), 1.58-1.68 (1H, m), 1.31-1.41 (1H, m). m/z (ESI, +ve) 376.3 (M+H)+:

Workup

  1. customSeparation of this material

Sources & evidence

ORD record
ord-7caad045317d4e019fec9f6e4d39d094
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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