Cyclohexylamine → 6-chloro-N-cyclohexyl-4-iodopyridin-2-amine
Reaction equation
[CH:1]1([NH2:7])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl:8][C:9]1[CH:14]=[C:13]([I:15])[CH:12]=[C:11](Cl)[N:10]=1>>[Cl:8][C:9]1[N:10]=[C:11]([NH:7][CH:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)[CH:12]=[C:13]([I:15])[CH:14]=1Participants
Procedure
Cyclohexanamine (4.0 mL, 34.9 mmol) was added to 2,6-dichloro-4-iodo-pyridine (954 mg, 3.48 mmol) in a microwave tube and subjected to 300 watts at 150° C. for 30 minutes in a Biotage Microwave Reactor. The crude product was partitioned with water, dichloromethane and the organics combined and concentrated to dryness. The residue was partially purified using silica gel flash chromatography eluting with 2% ethyl acetate, 98% hexanes to give 916 mg 6-chloro-N-cyclohexyl-4-iodopyridin-2-amine as a purple gum. This material was dissolved in 15 mL DMF and 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (666 mg, 1.98 mmol) added followed by addition of potassium acetate (400 mg, 4.07 mmol). The mixture was degassed with nitrogen and 1,1′-bis(diphenylphosphino)-ferrocene)dichloropalladium(II) complex with dichloromethane (222 mg, 0.272 mmol) added and the reaction mixture heated at 75° C. for 4 hours and then cooled to room temperature and partitioned with water, ethyl acetate. The organics were combined, concentrated to dryness and purified by silica gel flash chromatography eluting with a gradient from 3% ethyl acetate, 97% hexanes to 6% ethyl acetate, 94% hexanes to provide the title compound as a clear gum in 73% yield. MS (DCI+) m/z 337.2 (M+H)+.
Workup
- customThe crude product was partitioned with water, dichloromethane
- concentrationconcentrated to dryness
- customThe residue was partially purified
- washeluting with 2% ethyl acetate, 98% hexanes
Sources & evidence
- ORD record
- ord-ef3caa09067e4fd680b23248a0953432
- Source dataset
- uspto-grants-2013_05
- Patent number
- US08435980B2
Reaction notes
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