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

HRID 2208956ノート

反応式

HRID 2208956 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:38])[NH:30][C:31]([CH3:37])=[CH:32][C:33]=1[CH2:34][CH2:35][CH3:36].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:14])[F:16])[CH:12]=1)[C:7]([NH:26][CH2:27][C:28]1[C:29](=[O:38])[NH:30][C:31]([CH3:37])=[CH:32][C:33]=1[CH2:34][CH2:35][CH3:36])=[O:8])[CH3:2]

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 708736533-[Ethyl(1-methylpiperidin-4-yl)amino]-2-methyl-5-(trifluoromethyl)benzoic acidHCID 708741233-AMinoMethyl-6-Methyl-4-propyl-1H-pyridin-2-one hydrochloride

生成物 1

HCID 708747773-[Ethyl(1-methylpiperidin-4-yl)amino]-2-methyl-N-[(6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl]-5-(trifluoromethyl)benzamide収率 22.4%

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, 680 mg, 1.97 mmol) and 3-(aminomethyl)-6-methyl-4-propyl-1,2-dihydropyridin-2-one HCl salt (642 mg, 2.96 mmol) in DMSO (7 mL) was added PyBOP (1.85 g, 3.55 mmol) and hunig base (764 mg, 5.91 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=20/1) to give the titled compound as a white solid (224 mg, 22% yield). 1H-NMR (400 MHz, CDCl3) δppm; 7.31 (s, 1H), 7.26 (s, 1H), 7.16 (m, 1H), 5.94 (s, 1H), 4.55 (d, J=5.9 Hz, 2H), 3.08 (q, J=7.0 Hz, 2H), 2.82 (m, 2H), 2.66-2.73 (m, 3H), 2.33 (s, 3H), 2.24 (s×2, 6H), 1.79-1.98 (m, 2H), 1.67-1.75 (m, 4H), 1.59-1.66 (m, 2H), 1.02 (t, J=7.2 Hz, 3H), 0.84 (t, J=7.0 Hz, 3H); MS (ES) [M−H] 505.2; HPLC 98.1% 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=20/1)

出典と根拠

ORDレコード
ord-904c61754a7548518d2abea74ccc9663
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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