Cesium carbonate → HCID 178423466, compound

HRID 1842489Notes

Reaction equation

C(=O)([O-])[O-].[Cs+].[Cs+].Cl.Cl.[NH:9]1[CH2:12][CH:11]([C:13]2[NH:17][C:16]3[CH:18]=[CH:19][C:20]([CH3:22])=[CH:21][C:15]=3[N:14]=2)[CH2:10]1.[Cl:23][C:24]1[C:25](F)=[N:26][CH:27]=[CH:28][CH:29]=1>CN1C(=O)CCC1>[Cl:23][C:24]1[C:25]([N:9]2[CH2:12][CH:11]([C:13]3[NH:17][C:16]4[CH:18]=[CH:19][C:20]([CH3:22])=[CH:21][C:15]=4[N:14]=3)[CH2:10]2)=[N:26][CH:27]=[CH:28][CH:29]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a mixture of cesium carbonate (435 mg, 1.34 mmol) and 2-(azetidin-3-yl)-5-methyl-1H-benzo[d]imidazole dihydrochloride (0.100 g, 0.384 mmol) was added NMP (1 mL) and 3-chloro-2-fluoropyridine (0.105 g, 0.798 mmol). The reaction mixture was degassed and heated to 100° C. for 1 h, then heated to 130° C. for 2 h. The reaction was diluted with EtOAc. The organic phase was washed with water (2×), brine (1×), dried over MgSO4, filtered, and concentrated. Purification by flash column chromatography on silica gel (30% to 90% EtOAc in hexanes) followed by purification by reverse phase HPLC (10% to 50% water/MeCN followed by neutralization of the TFA salt with saturated NaHCO3) gave 2-(1-(3-chloropyridin-2-yl)azetidin-3-yl)-5-methyl-1H-benzo[d]imidazole (0.011 g, 0.037 mmol, 10% yield) as a dark yellow foam.

Workup

customThe reaction mixture was degassed
temperatureheated to 130° C. for 2 h
additionThe reaction was diluted with EtOAc
washThe organic phase was washed with water (2×), brine (1×)
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated
customPurification by flash column chromatography on silica gel (30% to 90% EtOAc in hexanes)
customfollowed by purification by reverse phase HPLC (10% to 50% water/MeCN

Sources & evidence

ORD record: ord-8b7f7a10813e427fbad829800161672d
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08946230B2

Reaction notes

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