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 2208961노트

반응식

HRID 2208961 반응식
[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]

참가 물질

6

반응물 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

생성물 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]benzamide수율 17.1%

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

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온도
23 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-c6d3803bc2d44a73a5c26b92ab39a90f
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09376422B2

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