Diisopropylethylamine → 2,6-dichloro-N-(tetrahydro-2H-pyran-4-yl)nicotinamide
Reaction equation
[Cl:1][C:2]1[N:10]=[C:9]([Cl:11])[CH:8]=[CH:7][C:3]=1[C:4](Cl)=[O:5].[NH2:12][CH:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1.C(N(C(C)C)C(C)C)C>C(Cl)Cl>[Cl:1][C:2]1[N:10]=[C:9]([Cl:11])[CH:8]=[CH:7][C:3]=1[C:4]([NH:12][CH:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1)=[O:5]Participants
Procedure
A solution of 2,6-dichloronicotinoyl chloride (4.21 g, 20 mmol) in DCM (20 mL) was added dropwise to a stirred suspension of 4-aminotetrahydropyran (2.03 g, 20 mmol) and N-ethyldiisopropylamine (4.19 mL, 24 mmol) in DCM (20 mL) at 0° C., over a period of 30 minutes under nitrogen. The resulting suspension was stirred at room temperature for 18 hours. The reaction mixture was diluted with DCM (200 mL), and washed sequentially with water (50 mL) and saturated brine (50 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in DCM. Pure fractions were evaporated to dryness to afford 2,6-dichloro-N-(tetrahydro-2H-pyran-4-yl)nicotinamide (5.03 g, 92%) as a white solid.
Workup
- washwashed sequentially with water (50 mL) and saturated brine (50 mL)
- dry with materialThe organic layer was dried over MgSO4
- filtrationfiltered
- customevaporated
- customto afford crude product
- customThe crude product was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in DCM
- customPure fractions were evaporated to dryness
Sources & evidence
- ORD record
- ord-805d32d8001d42c6869f678b2b9cfb1a
- Source dataset
- uspto-grants-2014_03
- Patent number
- US08673938B2
Reaction notes
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