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 42436Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 42436
[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]

Komponenten

8

Edukt 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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

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]+.

Aufarbeitung

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

Quellen und Nachweise

ORD-Eintrag
ord-98440bfd3526434999dcee7ba193241f
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08536179B2

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