1,2-Dichloroethane → N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-6-(4-((dimethylamino)methyl)piperidin-1-yl)-1-isopropyl-3-methyl-1H-indole-4-carboxamide

HRID 42420노트

반응식

HRID 42420 반응식
[CH3:1][N:2]([CH2:4][CH:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH:12]=[C:13]([C:24](O)=[O:25])[C:14]3[C:15]([CH3:23])=[CH:16][N:17]([CH:20]([CH3:22])[CH3:21])[C:18]=3[CH:19]=2)[CH2:7][CH2:6]1)[CH3:3].[NH2:27][CH2:28][C:29]1[C:30](=[O:37])[NH:31][C:32]([CH3:36])=[CH:33][C:34]=1[CH3:35].CN1CCOCC1.ON1C2N=CC=CC=2N=N1.C(Cl)CCl>CS(C)=O>[CH3:35][C:34]1[CH:33]=[C:32]([CH3:36])[NH:31][C:30](=[O:37])[C:29]=1[CH2:28][NH:27][C:24]([C:13]1[C:14]2[C:15]([CH3:23])=[CH:16][N:17]([CH:20]([CH3:21])[CH3:22])[C:18]=2[CH:19]=[C:11]([N:8]2[CH2:9][CH2:10][CH:5]([CH2:4][N:2]([CH3:1])[CH3:3])[CH2:6][CH2:7]2)[CH:12]=1)=[O:25]

참가 물질

7

반응물 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 181649HOAtHCID 70638443-(Aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-oneHCID 674659296-(4-((Dimethylamino)methyl)piperidin-1-yl)-1-isopropyl-3-methyl-1H-indole-4-carboxylic acid

생성물 1

HCID 54670171N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-6-(4-((dimethylamino)methyl)piperidin-1-yl)-1-isopropyl-3-methyl-1H-indole-4-carboxamide수율 61.1%

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

실험 절차

To a solution of 6-{-4-[(dimethylamino)methyl]-1-piperidinyl}-3-methyl-1-(1-methylethyl)-1H-indole-4-carboxylic acid (62 mg, 0.173 mmol) in dimethyl sulfoxide (1 mL) were added 3-(aminomethyl)-4,6-dimethyl-2(1H)-pyridinone (42.5 mg, 0.225 mmol), N-methylmorpholine (0.095 mL, 0.867 mmol), 1-hydroxy-7-azabenzotriazole (47.2 mg, 0.347 mmol) and EDC (66.5 mg, 0.347 mmol), and the mixture was stirred overnight. The mixture was purified using reverse-phase HPLC (Gemini 5u C18(2) 100A, AXIA; 30×100 mm 5 micron; 30 mL/min, 8% ACN/H2O, 0.1% formic acid to 38% ACN/H2O, 0.1% formic acid) to give the title compound (52 mg, 55%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) ppm 1.26 (m, 2H), 1.35-1.41 (m, 6H), 1.57-1.71 (m, 1H), 1.80 (d, J=11.12 Hz, 2H), 2.10 (d, J=10.36 Hz, 6H), 2.22 (s, 3H), 2.26-2.33 (m, 8H), 2.57-2.72 (m, 2H), 3.61 (d, J=12.13 Hz, 2H), 4.31 (d, J=5.05 Hz, 2H), 4.58-4.72 (m, 1H), 5.86 (s, 1H), 6.69 (d, J=2.02 Hz, 1H), 6.92 (d, J=1.77 Hz, 1H), 7.05 (d, J=1.01 Hz, 1H), 7.92-7.99 (m, 1H). MS: (M+H)+=492.1.

후처리

  1. customThe mixture was purified

출처 및 근거

ORD 기록
ord-544fab5fb93349b5b3f0f070e69316ae
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08536179B2

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