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

HRID 2208961ノート

反応式

HRID 2208961 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([N:12]([CH2:20][CH3:21])[CH:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)[C:5]([CH3:11])=[C:6]([CH:10]=1)[C:7]([OH:9])=O.Cl.[NH2:23][CH2:24][C:25]1[C:26](=[O:35])[NH:27][C:28]([CH3:34])=[CH:29][C:30]=1[CH2:31][CH2:32][CH3:33].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>[Cl:1][C:2]1[CH:3]=[C:4]([N:12]([CH2:20][CH3:21])[CH:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)[C:5]([CH3:11])=[C:6]([CH:10]=1)[C:7]([NH:23][CH2:24][C:25]1[C:26](=[O:35])[NH:27][C:28]([CH3:34])=[CH:29][C:30]=1[CH2:31][CH2:32][CH3:33])=[O:9]

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 708738575-Chloro-3-[ethyl(1-methylpiperidin-4-yl)amino]-2-methylbenzoic acidHCID 708741233-AMinoMethyl-6-Methyl-4-propyl-1H-pyridin-2-one hydrochloride

生成物 1

HCID 708746185-Chloro-3-[ethyl(1-methylpiperidin-4-yl)amino]-2-methyl-N-[(6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl]benzamide収率 17.1%

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 5-chloro-3-[ethyl(1-methylpiperidin-4-yl)amino]-2-methylbenzoic acid (crude material, 1.80 g, 3.26 mmol) and 3-(aminomethyl)-6-methyl-4-propyl-1,2-dihydropyridin-2-one HCl salt (916 mg, 4.24 mmol) in DMSO (10 mL) was added PyBOP (3.10 g, 5.87 mmol) and hunig base (1.20 g, 9.78 mmol). The reaction mixture was stirred at 23° C. for 16 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=10/1) to give the titled compound as a white solid (264 mg, 17% yield). 1H-NMR (400 MHz, CDCl3) δppm; 7.20 (t, J=5.9 Hz, 1H), 7.06 (d, J=2.0 Hz, 1H), 7.02 (d, J=2.0 Hz, 1H), 5.96 (s, 1H), 4.54 (d, J=5.9 Hz, 2H), 3.02 (q, J=7.0 Hz, 2H), 2.81 (m, 2H), 2.64-2.71 (m, 3H), 2.21-2.27 (s×3, 9H), 1.84-1.94 (m, 2H), 1.55-1.65 (m, 6H), 1.00 (t, J=7.4 Hz, 3H), 0.84 (t, J=7.0 Hz, 3H); MS (ES) [M+H] 473.1, [M+Na] 495.3; HPLC 94.7% 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=10/1)

出典と根拠

ORDレコード
ord-c6d3803bc2d44a73a5c26b92ab39a90f
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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