Isopropanol → 1-(3-((1-(Quinolin-2-YL)piperidin-4-YL)oxy)pyrazin-2-YL)piperidin-4-OL

HRID 454915Notes

Reaction equation

Cl[C:2]1[C:3]([O:8][CH:9]2[CH2:14][CH2:13][N:12]([C:15]3[CH:24]=[CH:23][C:22]4[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=4)[N:16]=3)[CH2:11][CH2:10]2)=[N:4][CH:5]=[CH:6][N:7]=1.[NH:25]1[CH2:30][CH2:29][CH:28]([OH:31])[CH2:27][CH2:26]1.C([O-])([O-])=O.[K+].[K+].C(O)(C)C>O>[N:16]1[C:17]2[C:22](=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:23]=[CH:24][C:15]=1[N:12]1[CH2:13][CH2:14][CH:9]([O:8][C:3]2[C:2]([N:25]3[CH2:30][CH2:29][CH:28]([OH:31])[CH2:27][CH2:26]3)=[N:7][CH:6]=[CH:5][N:4]=2)[CH2:10][CH2:11]1

Participants

Conditions

Temperature: 160 °C

Procedure

To a mixture of 2-(4-((3-chloropyrazin-2-yl)oxy)piperidin-1-yl)quinoline (see PREPARATION P1.1; 0.1 g, 0.29 mmol) and piperidin-4-ol (0.029 g, 0.29 mmol) and K2CO3 (0.08 g, 0.58 mmol) was added isopropyl alcohol (i-PrOH) (2 mL) and water (0.5 ml). The solution was heated to 160° C. under microwave for 5 hours. Then the mixture was concentrated and extracted with EtOAc (2×20 mL). The combined organic extracts were washed with water (10 mL) and brine (10 mL), dried over Na2SO4, and filtered. The filtrate was evaporated in vacuo and the residue was purified by flash column chromatography on silica gel (20% to 60% EtOAc in petroleum ether) to give the title product (0.02 g, 0.04 mmol, 17% yield) as white solid. ESI-MS (M+1): 406 calc. for C23H27N5O2 405.

Workup

concentrationThen the mixture was concentrated
extractionextracted with EtOAc (2×20 mL)
washThe combined organic extracts were washed with water (10 mL) and brine (10 mL)
dry with materialdried over Na2SO4
filtrationfiltered
customThe filtrate was evaporated in vacuo
customthe residue was purified by flash column chromatography on silica gel (20% to 60% EtOAc in petroleum ether)

Sources & evidence

ORD record: ord-68a81750f9fb49929012f7b52d471e29
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08497265B2

Reaction notes

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