Water → 5-(1-(6-Fluoroquinolin-2-YL)piperidin-4-YL)-7,7-dimethyl-5H-pyrrolo[2,3-B]pyrazin-6(7H)-one

HRID 707395Notes

Reaction equation

Cl.[CH3:2][C:3]1([CH3:19])[C:11]2[C:6](=[N:7][CH:8]=[CH:9][N:10]=2)[N:5]([CH:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)[C:4]1=[O:18].FC(F)(F)S(O[C:26]1[CH:35]=[CH:34][C:33]2[C:28](=[CH:29][CH:30]=[C:31]([F:36])[CH:32]=2)[N:27]=1)(=O)=O.CCN(C(C)C)C(C)C.O>CS(C)=O>[F:36][C:31]1[CH:32]=[C:33]2[C:28](=[CH:29][CH:30]=1)[N:27]=[C:26]([N:15]1[CH2:16][CH2:17][CH:12]([N:5]3[C:6]4=[N:7][CH:8]=[CH:9][N:10]=[C:11]4[C:3]([CH3:19])([CH3:2])[C:4]3=[O:18])[CH2:13][CH2:14]1)[CH:35]=[CH:34]2

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of 7,7-dimethyl-5-(piperidin-4-yl)-5H-pyrrolo[2,3-b]pyrazin-6(7H)-one hydrochloride (Intermediate 78) (0.117 g, 0.414 mmol), 6-fluoroquinolin-2-yl trifluoromethanesulfonate (0.134 g, 0.455 mmol), and DIEA (0.253 ml, 1.448 mmol) in DMSO (3 mL) was heated at 110° C. in 1 h. The reaction mixture was cooled, H2O was added, and the mixture was extracted with DCM (3×). The organic extracts were dried over Na2SO4, filtered, concentrated, and purified by ISCO (0-30% EtOAc/DCM) to give the title compound (81 mg, 50%). MS (M+1): 392.1. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.11-8.13 (1 H, m), 8.08-8.10 (1 H, m), 8.05 (1 H, d, J=9.2 Hz), 7.60 (1 H, dd, J=9.2, 5.3 Hz), 7.52 (1 H, dd, J=9.4, 2.9 Hz), 7.40-7.45 (1 H, m), 7.35-7.40 (1 H, m), 4.71 (2 H, d, J=13.5 Hz), 4.48-4.63 (1 H, m), 3.02 (2 H, t, J=12.1 Hz), 2.36-2.48 (2 H, m), 1.79 (2 H, d, J=9.8 Hz), 1.27-1.36 (6 H, m).

Workup

temperatureThe reaction mixture was cooled
extractionthe mixture was extracted with DCM (3×)
dry with materialThe organic extracts were dried over Na2SO4
filtrationfiltered
concentrationconcentrated
custompurified by ISCO (0-30% EtOAc/DCM)

Sources & evidence

ORD record: ord-fae9ce833089428892fd99a65710014b
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09174992B2

Reaction notes

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