Diisopropylethylamine → N-[(4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-3-[ethyl(1-methylpiperidin-4-yl)amino]-2-methyl-5-(trifluoromethyl)benzamide

HRID 2208955Notes

Reaction equation

HRID 2208955 reaction equation
[CH2:1]([N:3]([CH:18]1[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]1)[C:4]1[C:5]([CH3:17])=[C:6]([CH:10]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:12]=1)[C:7](O)=[O:8])[CH3:2].Cl.[NH2:26][CH2:27][C:28]1[C:29](=[O:36])[NH:30][C:31]([CH3:35])=[CH:32][C:33]=1[CH3:34].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CS(C)=O>[CH3:34][C:33]1[CH:32]=[C:31]([CH3:35])[NH:30][C:29](=[O:36])[C:28]=1[CH2:27][NH:26][C:7](=[O:8])[C:6]1[CH:10]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:12]=[C:4]([N:3]([CH2:1][CH3:2])[CH:18]2[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]2)[C:5]=1[CH3:17]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 438104513-(Aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-one hydrochlorideHCID 708736533-[Ethyl(1-methylpiperidin-4-yl)amino]-2-methyl-5-(trifluoromethyl)benzoic acid

Product 1

HCID 70913333N-[(4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-3-[ethyl(1-methylpiperidin-4-yl)amino]-2-methyl-5-(trifluoromethyl)benzamideYield 48%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
23 °C

Procedure

To a stirred solution of 3-[ethyl(1-methylpiperidin-4-yl)amino]-2-methyl-5-(trifluoromethyl)benzoic acid (crude material, 580 mg, 1.68 mmol) and 3-(aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-one HCl salt (477 mg, 2.53 mmol) in DMSO (6 mL) was added PyBOP (1.57 g, 3.02 mmol) and hunig base (650 mg, 5.04 mmol). The reaction mixture was stirred at 23° C. for 20 hours. The reaction mixture was quenched with water and resulting precipitate was collected. The solid was purified by silica gel column chromatography (NH—SiO2 ethylacetate/MeOH=25/1) to give the titled compound as a white amorphous (386 mg, 48% yield). 1HNMR (400 MHz, CDCl3) δppm; 7.31 (s, 1H), 7.27 (s, 1H), 7.18 (t, J=5.7 Hz, 1H), 5.95 (s, 1H), 4.55 (d, J=5.9 Hz, 2H), 3.17 (dq, J=6.4, 3.3 Hz, 2H), 3.08 (q, J=7.0 Hz, 2H), 2.81 (m, 2H), 2.70 (m, 1H), 2.40 (s, 3H), 2.33 (s, 3H), 2.23 (s, 3H), 2.21 (s, 3H), 1.78-1.93 (m, 2H), 1.70 (m, 2H), 0.84 (t, J=7.0 Hz, 3H); MS (ES) [M+H] 479.2, [M+Na] 501.3; HPLC 96.8% purity.

Workup

  1. customThe reaction mixture was quenched with water
  2. customresulting precipitate
  3. customwas collected
  4. customThe solid was purified by silica gel column chromatography (NH—SiO2 ethylacetate/MeOH=25/1)

Sources & evidence

ORD record
ord-dec10498c0f9439e833f451ecdd43cb5
Source dataset
uspto-grants-2016_06
Patent number
US09376422B2

Reaction notes

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