Tetrahydrofuran → 6-Chloro-N-(2-methylbut-3-yn-2-yl)pyridine-3-carboxamide
Reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][N:3]=1.C([N:13]([CH2:16][CH3:17])CC)C.[CH3:18]S(Cl)(=O)=O.[CH2:23]1COC[CH2:24]1>>[CH3:18][C:16]([NH:13][C:6](=[O:8])[C:5]1[CH:9]=[CH:10][C:2]([Cl:1])=[N:3][CH:4]=1)([CH3:17])[C:23]#[CH:24]Participants
Conditions
- Temperature
- -20 °C
Procedure
A 500 ml three neck flask was equipped with a mechanical stirrer, a thermometer, addition funnel, a gas inlet and a cooling bath. 6-Chloronicotinic acid (15.0 gm, 0.095 mole) along with dry THF (150 ml) was placed in this flask and was cooled to about -20° C. under a nitrogen atmosphere. Triethylamine (9.8 gm, 0.10 mole) was added in one portion, followed by the dropwise addition of methanesulfonyl chloride (11.4 gm, 0.01 mole) while maintaining the reaction mixture at -10° to -20° C. Upon complete addition of methanesulfonyl chloride, the mixture was stirred at about -20° C. for one hour. 1,1-Dimethylpropargyl amine (11.9 gm, 0.14 mole) was added gradually while keeping the reaction mixture below -10° C., then was stirred at this temperature for 1 hour. The resulting product was processed in a manner analogous to that described in example 3a. Recrystallization of the crude product from a mixture of hexane and methylene chloride (95:5) afforded 19 gm pure product.
Workup
- additiona thermometer, addition funnel, a gas inlet and a cooling bath
- temperaturewhile maintaining the reaction mixture at -10° to -20° C
- customthe reaction mixture below -10° C.
- stirringwas stirred at this temperature for 1 hour
- customRecrystallization of the crude product
- additionfrom a mixture of hexane and methylene chloride (95:5)
Sources & evidence
- ORD record
- ord-0c2717e7c8c744c5b9990df3c446be91
- Source dataset
- uspto-grants-1996_06
- Patent number
- US05529978
Reaction notes
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