Cesium carbonate → HCID 178503266, compound

HRID 724302Notes

Reaction equation

Cl[C:2]1[N:17]=[CH:16][C:15]([F:18])=[CH:14][C:3]=1[C:4]([NH:6][C@H:7]1[CH2:12][CH2:11][C@H:10]([OH:13])[CH2:9][CH2:8]1)=[O:5].[CH3:19][S:20][C:21]1[CH:26]=[CH:25][C:24]([OH:27])=[CH:23][CH:22]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[F:18][C:15]1[CH:16]=[N:17][C:2]([O:27][C:24]2[CH:25]=[CH:26][C:21]([S:20][CH3:19])=[CH:22][CH:23]=2)=[C:3]([CH:14]=1)[C:4]([NH:6][C@H:7]1[CH2:12][CH2:11][C@H:10]([OH:13])[CH2:9][CH2:8]1)=[O:5]

Participants

Conditions

Temperature: 55 °C

Procedure

2-Chloro-5-fluoro-N-(trans-4-hydroxy-cyclohexyl)-nicotinamide (150 mg, 0.55 mmol), 4-methylsulfanyl-phenol (77 mg, 0.55 mmol) and caesium carbonate (358 mg, 1.10 mmol) were suspended in DMF (2 ml) and the reaction was heated to 55° C. and stirred at this temperature under nitrogen for 18 h. The reaction was quenched with sat. ammonium chloride solution (1.5 ml) and water (1.5 ml) and the organic phase was collected by passing the mixture through a chemelute cartridge, washing with ethyl acetate. The solvent was removed on a Genevac™ and the residue was purified by flash column chromatography on silica gel eluting with a solvent gradient of dichloromethane:methanol (100:0 changing to 96:4, by volume) to give 5-fluoro-N-(trans-4-hydroxy-cyclohexyl)-2-(4-methylsulfanyl-phenoxy)-nicotinamide (81 mg) as an off-white foam.

Workup

customThe reaction was quenched with sat. ammonium chloride solution (1.5 ml) and water (1.5 ml)
customthe organic phase was collected
washwashing with ethyl acetate
customThe solvent was removed on a Genevac™
customthe residue was purified by flash column chromatography on silica gel eluting with a solvent gradient of dichloromethane:methanol (100:0 changing to 96:4, by volume)

Sources & evidence

ORD record: ord-e1354e8a909040abb25488ea495bfc37
Source dataset: uspto-grants-2006_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07141586B2

Reaction notes

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