Dimethyl Sulfoxide → (1H-benzoimidazol-2-yl)-{3-[3-(4-hydroxy-piperidin-1-yl)-pyrazin-2-yl]-azetidin-1-yl}-methanone

HRID 1850334Notes

Reaction equation

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

Participants

Conditions

Temperature: 120 °C

Procedure

To a mixture of (1H-benzoimidazol-2-yl)-[3-(3-chloro-pyrazin-2-yl)-azetidin-1-yl]-methanone (0.170 g, 0.50 mmol) and piperidin-4-ol (0.101 g, 1.0 mmol) was added triethylamine (0.10 g, 1.0 mmol) and DMSO (4 mL). The solution was heated to 120° C. for 4 h. Then the mixture was diluted with water (10 mL) 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 50% EtOAc in petroleum ether) to give (1H-benzoimidazol-2-yl)-{3-[3-(4-hydroxy-piperidin-1-yl)-pyrazin-2-yl]-azetidin-1-yl}-methanone (0.16 g, 0.42 mmol, 85% yield) as a white solid.

Workup

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 50% EtOAc in petroleum ether)

Sources & evidence

ORD record: ord-89389f856d074c97beb1384e87f9cbe0
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08957073B2

Reaction notes

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