Triethylamine → N-{[4-cyano-2-(trifluoromethyl)phenyl]methyl}-1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]-4-piperidinecarboxamide

HRID 1678450Notes

Reaction equation

HRID 1678450 reaction equation
[CH3:1][C:2]1[N:7]=[C:6]([NH:8][CH3:9])[N:5]=[C:4]([N:10]2[CH2:15][CH2:14][CH:13]([C:16]([OH:18])=O)[CH2:12][CH2:11]2)[N:3]=1.CCN=C=N[CH2:24][CH2:25][CH2:26][N:27](C)C.C1[CH:31]=[CH:32][C:33]2N(O)N=[N:36][C:34]=2C=1.[CH2:40](N(CC)CC)C.BrC1C=CC(CN)=C(O[C:57]([F:60])([F:59])[F:58])C=1>ClCCl>[C:26]([C:25]1[CH:24]=[CH:40][C:33]([CH2:34][NH:36][C:16]([CH:13]2[CH2:12][CH2:11][N:10]([C:4]3[N:3]=[C:2]([CH3:1])[N:7]=[C:6]([NH:8][CH3:9])[N:5]=3)[CH2:15][CH2:14]2)=[O:18])=[C:32]([C:57]([F:60])([F:59])[F:58])[CH:31]=1)#[N:27]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 594477131-[4-Methyl-6-(methylamino)-1,3,5-triazin-2-yl]-4-piperidinecarboxylic acidHCID 59447718(4-Bromo-2-(trifluoromethoxy)phenyl)methanamine

Product 1

HCID 25261292N-{[4-cyano-2-(trifluoromethyl)phenyl]methyl}-1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]-4-piperidinecarboxamideYield 5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]-4-piperidinecarboxylic acid (100 mg, 0.4 mmol) was dissolved in 3 mL of dichloromethane and treated with EDCI (115 mg, 0.6 mmol), HOBt (65 mg, 0.48 mmol), triethylamine (0.44 mL, 3.2 mmol), and 1-{4-bromo-2-[(trifluoromethyl)oxy]phenyl}methanamine (152 mg, 0.4 mmol) at 8° C. for 4 days. The reaction mixture was concentrated and purified by preparative HPLC to provide N-{[4-cyano-2-(trifluoromethyl)phenyl]methyl}-1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]-4-piperidinecarboxamide (3.5 mg, 0.02 mmol, 2%) as a white solid. MS (ES+): m/e 503, 505 [M+H]+. 1H NMR (400 MHz, methanol-D4) 7.4 (m, 2H), 7.2 (d, 1H), 4.8 (2H under MeOH peak), 4.3 (s, 2H), 3.1 (m, 2H), 2.9 (s, 3H), 2.5 (m, 1H), 2.3 (s, 3H), 1.8 (m, 2H), 1.6 (m, 2H)

Workup

  1. concentrationThe reaction mixture was concentrated
  2. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-2f9191f159c344dfa7129a1fdd07100c
Source dataset
uspto-grants-2011_08
Patent number
US08008483B2

Reaction notes

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