1,2-Dichloroethane → tert-butyl (5-((6-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxamido)methyl)-6-methoxy-4-methylpyridin-2-yl)carbamate

HRID 593808노트

반응식

HRID 593808 반응식
[NH2:1][CH2:2][C:3]1[C:4]([CH3:19])=[CH:5][C:6]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[N:7][C:8]=1[O:9][CH3:10].[Br:20][C:21]1[CH:22]=[C:23]([C:34](O)=[O:35])[C:24]2[C:25]([CH3:33])=[CH:26][N:27]([CH:30]([CH3:32])[CH3:31])[C:28]=2[CH:29]=1.C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C>[Br:20][C:21]1[CH:22]=[C:23]([C:34]([NH:1][CH2:2][C:3]2[C:4]([CH3:19])=[CH:5][C:6]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:15])([CH3:16])[CH3:17])=[N:7][C:8]=2[O:9][CH3:10])=[O:35])[C:24]2[C:25]([CH3:33])=[CH:26][N:27]([CH:30]([CH3:31])[CH3:32])[C:28]=2[CH:29]=1

참가 물질

6

반응물 4

HCID 111,2-DichloroethaneHCID 181649HOAtHCID 674686786-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxylic acidHCID 71276137Tert-butyl (5-(aminomethyl)-6-methoxy-4-methylpyridin-2-yl)carbamate

생성물 1

HCID 71274276tert-butyl (5-((6-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxamido)methyl)-6-methoxy-4-methylpyridin-2-yl)carbamate수율 99.9%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a stirred solution of tert-butyl (5-(aminomethyl)-6-methoxy-4-methylpyridin-2-yl)carbamate (0.40 g, 1.496 mmol), 6-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxylic acid (0.44 g, 1.486 mmol), and HOAt (0.21 g, 1.543 mmol) in DMF (25 mL) was added EDC free base (0.25 g, 1.610 mmol). The reaction was stirred at RT overnight then evaporated to dryness under vacuum. The remaining was purified by silica gel chromatography (Analogix, SF25-60g, 0 to 30% EtOAc in hexanes) to give the product tert-butyl (5-((6-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxamido)methyl)-6-methoxy-4-methylpyridin-2-yl)carbamate (0.81 g, 1.485 mmol, 99% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ=9.42 (s, 1H), 8.41 (t, J=4.8 Hz, 1H), 7.77 (d, J=1.5 Hz, 1H), 7.33 (s, 1H), 7.21 (s, 1H), 6.99 (d, J=1.8 Hz, 1H), 4.40 (d, J=5.1 Hz, 2H), 3.81 (s, 3H), 2.35 (s, 3H), 2.10 (d, J=1.0 Hz, 3H), 1.47 (s, 9H), 1.38 (d, J=6.6 Hz, 6H). MS(ES)+ m/e 545.2 [M+H]+.

후처리

  1. customthen evaporated to dryness under vacuum
  2. customThe remaining was purified by silica gel chromatography (Analogix, SF25-60g, 0 to 30% EtOAc in hexanes)

출처 및 근거

ORD 기록
ord-8c36e367d5294846b5bd0d0bfc09e7f2
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09242962B2

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