Ethyl Acetate → 5-chloro-1-[(2,2-difluoro-1-methylcyclopropyl)methyl]-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one
Reaction equation
[Cl:1][C:2]1[N:7]=[C:6]2[N:8]([CH3:16])[C:9](=[O:15])[N:10]([CH2:11]C(C)=C)[C:5]2=[CH:4][CH:3]=1.Cl[C:18]([F:23])([F:22])[C:19](O)=O.[Na].C(O[CH2:29][CH3:30])(=O)C>C(=O)(O)[O-].[Na+]>[Cl:1][C:2]1[N:7]=[C:6]2[N:8]([CH3:16])[C:9](=[O:15])[N:10]([CH2:11][C:29]3([CH3:30])[CH2:19][C:18]3([F:23])[F:22])[C:5]2=[CH:4][CH:3]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 200 °C
Procedure
5-chloro-3-methyl-1-(2-methylprop-2-en-1-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (74-1) (6 g, 25.2 mmol) was added to a round bottom flask along with chloro(difluoro)acetic acid-sodium (1:1) (38.42 g, 252 mmol) this was mixed together with a spatula then heated to 200° C. for one hour. The reaction was then cooled to room temperature and suspended in ethyl acetate and sodium bicarbonate. The suspension was washed with sodium bicarbonate, brine (×5), dried over sodium sulfate, filtered, and concentrated. The mixture was purified using normal phase chromatography (0-60% Ethyl Acetate/Hexanes), and the desired fractions were collected to produce the solid 5-chloro-1-[(2,2-difluoro-1-methylcyclopropyl)methyl]-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (74-2). HRMS (M+H)+: observed=288.0713, calculated=288.0715.
Workup
- additionthis was mixed together with a spatula
- temperatureThe reaction was then cooled to room temperature
- washThe suspension was washed with sodium bicarbonate, brine (×5)
- dry with materialdried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated
- customThe mixture was purified
- customthe desired fractions were collected
Sources & evidence
- ORD record
- ord-906c6656e2a04309844287b57a96edfb
- Source dataset
- uspto-grants-2014_07
- Patent number
- US08765784B2
Reaction notes
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