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 2208955ノート

反応式

HRID 2208955 の反応式
[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]

参加物

6

反応物 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

生成物 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)benzamide収率 48%

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

反応条件

温度
23 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-dec10498c0f9439e833f451ecdd43cb5
出典データセット
uspto-grants-2016_06
特許番号
US09376422B2

反応ノート

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