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

HRID 2208958Notes

Reaction equation

HRID 2208958 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]([OH:9])=O)[CH3:2].Cl.Cl.[NH2:27][CH2:28][C:29]1[C:30](=[O:40])[NH:31][C:32]([CH3:39])=[CH:33][C:34]=1[C:35]([F:38])([F:37])[F:36].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>[CH2:1]([N:3]([CH:18]1[CH2:19][CH2:20][N:21]([CH3:24])[CH2:22][CH2:23]1)[C:4]1[C:5]([CH3:17])=[C:6]([CH:10]=[C:11]([C:13]([F:15])([F:16])[F:14])[CH:12]=1)[C:7]([NH:27][CH2:28][C:29]1[C:30](=[O:40])[NH:31][C:32]([CH3:39])=[CH:33][C:34]=1[C:35]([F:36])([F:37])[F:38])=[O:9])[CH3:2]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 708736533-[Ethyl(1-methylpiperidin-4-yl)amino]-2-methyl-5-(trifluoromethyl)benzoic acidHCID 901508353-(Aminomethyl)-6-methyl-4-(trifluoromethyl)-1,2-dihydropyridin-2-one hydrochloride HCl salt

Product 1

HCID 890527413-[Ethyl(1-methylpiperidin-4-yl)amino]-2-methyl-N-{[6-methyl-2-oxo-4-(trifluoromethyl)-1,2-dihydropyridin-3-yl]methyl}-5-(trifluoromethyl)benzamideYield 45%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a stirred solution of 3-[ethyl(1-methylpiperidin-4-yl)amino]-2-methyl-5-(trifluoromethyl)benzoic acid (crude material, ˜0.313 mmol) and 3-(aminomethyl)-6-methyl-4-(trifluoromethyl)-1,2-dihydropyridin-2-one hydrochloride HCl salt (100 mg, 0.91 mmol) in DMSO (2.4 mL) was added PyBOP (248 mg, 1.05 mmol) and hunig base (166 ul, 2.10 mmol). The reaction mixture was stirred at rt for 16 hours. The reaction mixture was quenched with water and resulting precipitate was collected. The solid was triturated from ethylacetate/hexane. The resulting solid was purified by silica gel column chromatography (NH—SiO2 ethylacetate/MeOH=10/1+10% triethylamine). The crude compound was triturated from ethylacetate/hexane, and dried to give the titled compound as a white solid (75.0 mg, 44% yield). 1H-NMR (400 MHz, CDCl3) δppm; 7.32 (s, 1H), 7.26 (s, 1H), 6.86-6.89 (m, 1H), 6.34 (s, 1H), 4.73 (d, J=6.4 Hz, 2H), 3.08 (q, J=7.2 Hz, 2H), 2.80-2.85 (m, 2H), 2.70-2.78 (m, 1H), 2.37 (s, 3H), 2.35 (s, 3H), 2.24 (s, 3H), 1.85-1.89 (m, 2H), 1.69-1.72 (m, 4H), 0.84 (t, J=7.2 Hz, 3H); MS (ES) [M+H] 533.1, [M+Na] 555.2; HPLC 95.8% purity.

Workup

  1. customThe reaction mixture was quenched with water
  2. customresulting precipitate
  3. customwas collected
  4. customThe solid was triturated from ethylacetate/hexane
  5. customThe resulting solid was purified by silica gel column chromatography (NH—SiO2 ethylacetate/MeOH=10/1+10% triethylamine)
  6. customThe crude compound was triturated from ethylacetate/hexane
  7. customdried

Sources & evidence

ORD record
ord-e9ea2235418c489cbc74463b732be540
Source dataset
uspto-grants-2016_06
Patent number
US09376422B2

Reaction notes

Loading…