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

HRID 42453Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 42453
Cl.[Cl:2][C:3]1[CH:4]=[C:5]([C:20](O)=[O:21])[C:6]2[C:7]([CH3:19])=[C:8]([CH2:15][N:16]([CH3:18])[CH3:17])[N:9]([CH:12]([CH3:14])[CH3:13])[C:10]=2[CH:11]=1.[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].C1C=NC2N(O)N=NC=2C=1.CN1CCOCC1.C(Cl)CCl>CN(C)C=O.ClCCl>[Cl:2][C:3]1[CH:4]=[C:5]([C:20]([NH:23][CH2:24][C:25]2[C:26](=[O:35])[NH:27][C:28]([CH3:34])=[CH:29][C:30]=2[CH2:31][CH2:32][CH3:33])=[O:21])[C:6]2[C:7]([CH3:19])=[C:8]([CH2:15][N:16]([CH3:18])[CH3:17])[N:9]([CH:12]([CH3:13])[CH3:14])[C:10]=2[CH:11]=1

Komponenten

8

Edukt 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 181649HOAtHCID 671241403-(Aminomethyl)-6-methyl-4-propylpyridin-2(1H)-oneacetateHCID 674684516-chloro-2-((dimethylamino)methyl)-1-isopropyl-3-methyl-1H-indole-4-carboxylic acid hydrochloride salt

Produkt 1

HCID 674642276-chloro-2-((dimethylamino)methyl)-1-isopropyl-3-methyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-1H-indole-4-carboxamideAusbeute 63,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To 6-chloro-2-((dimethylamino)methyl)-1-isopropyl-3-methyl-1H-indole-4-carboxylic acid hydrochloride salt (0.42 g, 1.216 mmol), 3-(aminomethyl)-6-methyl-4-propylpyridin-2(1H)-one (0.22 g, 1.221 mmol), HOAt (0.17 g, 1.249 mmol) was added Dichloromethane (16 mL), N,N-Dimethylformamide (4 mL) and N-methylmorpholine (135 μL, 1.228 mmol). The mixture was stirred and EDC free base (0.20 g, 1.288 mmol) was added. After stirring for 2 hr LCMS showed that the reaction was complete. The reaction was evaporated to dryness under vacuum and purified by silica gel chromatography (Analogix, SF25-60 g, 0 to 8% (5% NH4OH in MeOH) in CH2Cl2). The pure fractions were combined, evaporated to dryness then taken up in 20% EtOAc in hexanes. Scratching crystallized out the product which was filtered and washed with hexanes to give the product 6-chloro-2-((dimethylamino)methyl)-1-isopropyl-3-methyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-1H-indole-4-carboxamide (362 mg, 0.769 mmol, 63.2% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ=11.49 (s, 1H), 8.24 (t, J=4.9 Hz, 1H), 7.61 (d, J=1.8 Hz, 1H), 6.83 (d, J=1.8 Hz, 1H), 5.89 (s, 1H), 4.91 (quin, J=7.0 Hz, 1H), 4.31 (d, J=5.1 Hz, 2H), 3.47 (s, 2H), 2.52 (2H under DMSO), 2.14 (s, 6H), 2.12 (s, 3H), 2.10 (s, 3H), 1.62-1.53 (m, 2H), 1.51 (d, J=7.1 Hz, 6H), 0.94 (t, J=7.3 Hz, 3H). MS (ES)+m/e 471.3 [M+H]+.

Aufarbeitung

  1. stirringAfter stirring for 2 hr LCMS
  2. customThe reaction was evaporated to dryness under vacuum
  3. custompurified by silica gel chromatography (Analogix
  4. customevaporated to dryness
  5. customScratching crystallized out the product which
  6. filtrationwas filtered
  7. washwashed with hexanes

Quellen und Nachweise

ORD-Eintrag
ord-5d5cde2001eb478ebcf28f6c3a95491f
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08536179B2

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