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

HRID 42436ノート

反応式

HRID 42436 の反応式
[C:1]([O:5][C:6](=[O:20])[NH:7][CH2:8][C:9]1[CH:14]=[C:13]([CH3:15])[C:12]([CH2:16][NH2:17])=[C:11]([O:18][CH3:19])[N:10]=1)([CH3:4])([CH3:3])[CH3:2].[Br:21][C:22]1[CH:23]=[C:24]([C:35](O)=[O:36])[C:25]2[C:26]([CH3:34])=[CH:27][N:28]([CH:31]([CH3:33])[CH3:32])[C:29]=2[CH:30]=1.C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl>ClCCl.CN(C=O)C.CCOC(C)=O>[C:1]([O:5][C:6](=[O:20])[NH:7][CH2:8][C:9]1[CH:14]=[C:13]([CH3:15])[C:12]([CH2:16][NH:17][C:35]([C:24]2[C:25]3[C:26]([CH3:34])=[CH:27][N:28]([CH:31]([CH3:32])[CH3:33])[C:29]=3[CH:30]=[C:22]([Br:21])[CH:23]=2)=[O:36])=[C:11]([O:18][CH3:19])[N:10]=1)([CH3:3])([CH3:4])[CH3:2]

参加物

8

反応物 4

HCID 111,2-DichloroethaneHCID 181649HOAtHCID 674686786-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxylic acidHCID 67951653Tert-butyl ((5-(aminomethyl)-6-methoxy-4-methylpyridin-2-yl)methyl)carbamate

生成物 1

HCID 68210118tert-butyl((5-((6-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxamido)methyl)-6-methoxy-4-methylpyridin-2-yl)methyl)carbamate収率 98%

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a stirred solution of tert-butyl((5-(aminomethyl)-6-methoxy-4-methylpyridin-2-yl)methyl)carbamate (0.55 g, 1.955 mmol), 6-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxylic acid (0.63 g, 2.127 mmol), and HOAt (0.27 g, 1.984 mmol) in Dichloromethane (20 mL) and DMF (5 mL) was added EDC free base (0.34 g, 2.190 mmol). The reaction was stirred at RT for 2 hr then evaporated to dryness under vacuum. The remaining was purified by silica gel chromatography (Analogix, SF25-60 g, 0 to 40% 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)methyl)carbamate (1.07 g, 1.912 mmol, 98% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ=8.47 (t, J=4.8 Hz, 1H), 7.76 (d, J=1.8 Hz, 1H), 7.35 (t, 1H), 7.33 (d, J=1.0 Hz, 1H), 6.99 (d, J=1.5 Hz, 1H), 6.67 (s, 1H), 4.74 (quin, J=6.6 Hz, 1H), 4.44 (d, J=4.8 Hz, 2H), 4.08 (d, J=6.3 Hz, 2H), 3.85 (s, 3H), 2.37 (s, 3H), 2.10 (s, 3H), 1.41 (s, 9H), 1.38 (d, J=6.6 Hz, 6H). MS (ES)+m/e 559.3 [M+H]+.

後処理

  1. customthen evaporated to dryness under vacuum
  2. customThe remaining was purified by silica gel chromatography (Analogix

出典と根拠

ORDレコード
ord-98440bfd3526434999dcee7ba193241f
出典データセット
uspto-grants-2013_09
特許番号
US08536179B2

反応ノート

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