Cesium carbonate → HCID 178423468, compound

HRID 1842497Notes

Reaction equation

C(=O)([O-])[O-].[Cs+].[Cs+].Cl[C:8]1[C:9]([N:14]2[CH2:17][CH:16]([C:18]3[NH:22][C:21]4[CH:23]=[CH:24][C:25]([CH3:27])=[CH:26][C:20]=4[N:19]=3)[CH2:15]2)=[N:10][CH:11]=[CH:12][N:13]=1.CN1C(=O)CCC1.[O:35]1[CH2:40][CH2:39][CH:38]([OH:41])[CH2:37][CH2:36]1>CCOC(C)=O>[CH3:27][C:25]1[CH:24]=[CH:23][C:21]2[NH:22][C:18]([CH:16]3[CH2:17][N:14]([C:9]4[C:8]([O:41][CH:38]5[CH2:39][CH2:40][O:35][CH2:36][CH2:37]5)=[N:13][CH:12]=[CH:11][N:10]=4)[CH2:15]3)=[N:19][C:20]=2[CH:26]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a mixture of cesium carbonate (0.223 g, 0.684 mmol) and 2-(1-(3-chloropyrazin-2-yl)azetidin-3-yl)-5-methyl-1H-benzo[d]imidazole (0.103 g, 0.344 mmol) was added NMP (1 mL) and tetrahydro-2H-pyran-4-ol (0.20 mL, 2.1 mmol). The reaction mixture was heated to 100° C. for 1 h, heated to 130° C. for 2 h, and heated to 150° C. for 21 h. The reaction was diluted with EtOAc, and the organic phase was washed with saturated NaHCO3 (1×), brine (1×), dried over MgSO4, filtered, and concentrated. Purification by flash column chromatography on silica gel (60% to 100% EtOAc in hexanes) gave 5-methyl-2-(1-(3-(tetrahydro-2H-pyran-4-yloxy)pyrazin-2-yl)azetidin-3-yl)-1H-benzo[d]imidazole (0.061 g, 0.17 mmol, 49% yield) as a pale yellow foam. [M+1] 366. IC50 (uM) 0.2388.

Workup

temperatureheated to 130° C. for 2 h
temperatureheated to 150° C. for 21 h
washthe organic phase was washed with saturated NaHCO3 (1×), brine (1×)
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated
customPurification by flash column chromatography on silica gel (60% to 100% EtOAc in hexanes)

Sources & evidence

ORD record: ord-31dc2bb62f9647d59550ceee9ee027b3
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08946230B2

Reaction notes

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