Pyridine → Tert-butyl 4-(methylsulfonyl)piperazine-1-carboxylate
Reaction equation
[CH3:1][S:2](Cl)(=[O:4])=[O:3].[C:6]([N:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1)([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7].N1C=CC=CC=1>ClCCl>[C:9]([O:8][C:6]([N:13]1[CH2:18][CH2:17][N:16]([S:2]([CH3:1])(=[O:4])=[O:3])[CH2:15][CH2:14]1)=[O:7])([CH3:12])([CH3:10])[CH3:11]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
1.3 mL of methanesulfonyl chloride was slowly added to a solution of 2 g of 1-Boc-piperazine and 1.3 mL of pyridine in 6 mL of dichloromethane at 0° C. The reaction mixture was allowed to warm to room temperature and stirred for 2 h while being monitored by TLC. Upon completion, the mixture was diluted with dichloromethane, washed with H2O, dried (MgSO4) and evaporated. Purified by silica gel chromatograph (20-100% ethyl acetate/hexane) to afford tert-butyl-4-(methylsulfonyl)piperazine-1-carboxylate. 930 mg of tert-butyl-4-(methylsulfonyl)piperazine-1-carboxylate was treated with 4N HCl in dioxane for 2 h. The reaction mixture was evaporated to give the HCl salt of 1-(methylsulfonyl)piperazine. Procedure F was performed using 50 mg of 6-chloro-N-(4-chloro-3-(pyridin-2-yl)phenyl)-2-methylnicotinamide, 69 mg of 1-(methylsulfonyl)piperazine and DEPA (1 eq) in 0.5 mL of BuOH. Purified by reverse phase HPLC to yield N-(4-chloro-3-(pyridin-2-yl)phenyl)-2-methyl-6-(4-(methylsulfonyl)piperazin-1-yl)nicotinamide. MS (Q1) 486.3 (M)+.
Workup
- washwashed with H2O
- dry with materialdried (MgSO4)
- customevaporated
- customPurified by silica gel chromatograph (20-100% ethyl acetate/hexane)
Sources & evidence
- ORD record
- ord-82b034dbb4264b958f03cf44bc56e4c9
- Source dataset
- uspto-grants-2011_02
- Patent number
- US07888364B2
Reaction notes
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