Cesium carbonate → 5-chloro-1-[(2,2-difluorocyclopropyl)methyl][1,3]thiazolo[5,4-b]pyridin-2(1H)-one
Reaction equation
[Cl:1][C:2]1[N:7]=[C:6]2[S:8][C:9](=[O:11])[NH:10][C:5]2=[CH:4][CH:3]=1.CN1C(=O)CCC1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:26][CH:27]1[CH2:29][C:28]1([F:31])[F:30]>C(OCC)(=O)C.O1CCOCC1>[Cl:1][C:2]1[N:7]=[C:6]2[S:8][C:9](=[O:11])[N:10]([CH2:26][CH:27]3[CH2:29][C:28]3([F:31])[F:30])[C:5]2=[CH:4][CH:3]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 95 °C
Procedure
To a round bottom flask was added 5-chloro[1,3]thiazolo[5,4-b]pyridin-2(1H)-one (1-4) (3.5 g, 19 mmol), anhydrous NMP (30 mL), anhydrous 1,4-dioxane (60 mL), cesium carbonate (12 g, 37 mmol), followed by 2-(bromomethyl)-1,1-difluorocyclopropane (3.4 g, 20 mmol). The reaction mixture was then heated to 95° C. while stirring in a hot oil bath for 18 hours. The crude reaction mixture was then cooled to room temperature, then suspended in ethyl acetate and washed with a saturated solution of sodium bicarbonate, followed by water, then brine, dried over sodium sulfate, filtered, and concentrated. The resulting residue was purified by silica gel chromatography (0-40% EtOAc/Hex) to give 5-chloro-1-[(2,2-difluorocyclopropyl)methyl][1,3]thiazolo[5,4-b]pyridin-2(1H)-one (1-5) as a tan solid. HRMS (M+H)+: observed=277.0008, calculated=277.0008.
Workup
- customThe crude reaction mixture
- temperaturewas then cooled to room temperature
- washwashed with a saturated solution of sodium bicarbonate
- dry with materialbrine, dried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated
- customThe resulting residue was purified by silica gel chromatography (0-40% EtOAc/Hex)
Sources & evidence
- ORD record
- ord-72bc047dd426416f89f9f4caa90f4931
- Source dataset
- uspto-grants-2015_02
- Patent number
- US08952005B2
Reaction notes
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