4-Piperidinecarboxylic acid → 1-[4-Methyl-6-(methylamino)-1,3,5-triazin-2-yl]-4-piperidinecarboxylic acid
Reaction equation
Cl[C:2]1[N:7]=[C:6](Cl)[N:5]=[C:4]([CH3:9])[N:3]=1.[CH3:10][NH2:11].[OH-].[Na+].[NH:14]1[CH2:19][CH2:18][CH:17]([C:20]([OH:22])=[O:21])[CH2:16][CH2:15]1>C(#N)C.O>[CH3:9][C:4]1[N:5]=[C:6]([NH:11][CH3:10])[N:7]=[C:2]([N:14]2[CH2:19][CH2:18][CH:17]([C:20]([OH:22])=[O:21])[CH2:16][CH2:15]2)[N:3]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
2,4-dichloro-6-methyl-1,3,5-triazine (5 g, 31 mmol) was dissolved in a 1:1 mixture of acetonitrile and water and treated with an aqueous solution of methyl amine (0.88 mL, 31 mmol) at a low temperature maintained by immersing the reaction flask in an ice bath. The pH of the reaction mixture was adjusted to 9-10 with 1M NaOH and the reaction was stirred for 30 minutes. Then, 4-piperidinecarboxylic acid (5 g, 39 mmol) was added and the pH was maintained between 9 and 10 with additions of 1M NaOH as needed. The reaction was allowed to warm to room temperature and stirred for one hour. The reaction mixture was then concentrated and purified by preparative HPLC to provide 1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]-4-piperidinecarboxylic acid (31 mmol, 100%) as a white solid. MS (ES) m/e 252 [M+H]+. 1H NMR (400 MHz, methanol-D4) 4.7 (m, 2H), 3.3 (s, 2H), 3.0 (s, 3H), 2.7 (m, 1H), 2.4 (s, 3H), 2.0 (m, 2H), 1.7 (m, 2H)
Workup
- temperaturemaintained
- stirringstirred for one hour
- concentrationThe reaction mixture was then concentrated
- custompurified by preparative HPLC
Sources & evidence
- ORD record
- ord-c8ce9dbea7d94ceab67cc3bd08fd237f
- Source dataset
- uspto-grants-2011_08
- Patent number
- US08008483B2
Reaction notes
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