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Dimethylformamide → tert-Butyl 4-(1-(3-(((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)carbamoyl)-2-methyl-1H-indol-1-yl)ethyl)piperidine-1-carboxylate

HRID 2206529
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 2206529
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]([N:16]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[C:18]([C:25](O)=[O:26])=[C:17]2[CH3:28])[CH3:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[NH2:30][CH2:31][C:32]1[C:33](=[O:41])[NH:34][C:35]([CH3:40])=[CH:36][C:37]=1[O:38][CH3:39].CN(C=O)C.CCN(C(C)C)C(C)C.CCOC(C(C#N)=NOC(N1CCOCC1)=[N+](C)C)=O.F[P-](F)(F)(F)(F)F>O>[CH3:39][O:38][C:37]1[CH:36]=[C:35]([CH3:40])[NH:34][C:33](=[O:41])[C:32]=1[CH2:31][NH:30][C:25]([C:18]1[C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[N:16]([CH:14]([CH:11]2[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:7])[CH2:13][CH2:12]2)[CH3:15])[C:17]=1[CH3:28])=[O:26]
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

7

Edukt 5

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 75951468(1-Cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphateHCID 89740341HCID 89740341, VerbindungHCID 1177807191H-Indole-3-carboxylic acid, 1-[1-[1-[(1,1-dimethylethoxy)carbonyl]-4-piperidinyl]ethyl]-2-methyl-

Produkt 1

HCID 117807734
tert-Butyl 4-(1-(3-(((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)carbamoyl)-2-methyl-1H-indol-1-yl)ethyl)piperidine-1-carboxylate
Ausbeute 65,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A 250 mL round bottom flask was charged with a magnetic stir bar, (R or S)-1-(1-(1-(tert-butoxycarbonyl)piperidin-4-yl)ethyl)-2-methyl-1H-indole-3-carboxylic acid (1.950 g, 5.05 mmol), 3-(aminomethyl)-4-methoxy-6-methylpyridin-2(1H)-one hydrochloride (2.065 g, 10.09 mmol), DMF (25.2 ml, 5.05 mmol), Hunig's base (3.52 ml, 20.18 mmol). The reaction mixture was cooled to 0° C. and COMU (2.16 g, 5.05 mmol) was added. The reaction was allowed to stir overnight to room temperature. The reaction mixture was diluted with water and extracted with EtOAc. The combined organic extract was washed with brine, dried with MgSO4, filtered and conc., in vacuo to afford the crude material which was purified via silica gel chromatography (120 g) using MeOH/ethyl acetate (1:5) as eluent to afford the title compound (1.86 g, 3.29 mmol, 65.3% yield). LCMS 537 (M+1)+ 1H NMR (400 MHz, DMSO-d6) δ=11.83-11.71 (m, 1H), 7.80 (br. s., 1H1), 7.73 (d, J=7.6 Hz, 1H), 7.62 (d, J=7.8 Hz, 1H), 7.06 (td, J=7.1, 14.4 Hz, 2H), 6.21 (s, 1H), 4.32 (br. s., 2H), 4.16 (br. s., 1H), 4.02 (br. s., 1H), 3.85 (s, 3H), 3.75 (br. s., 1H), 2.70 (br. s., 1H), 2.58 (s, 3H), 2.37 (br. s., 1H), 2.21 (s, 3H), 1.90 (d, J=12.9 Hz, 1H), 1.53 (d, J=6.9 Hz, 3H), 1.35 (s, 10H), 1.21 (br. s., 1H), 0.89 (d, J=8.7 Hz, 1H), 0.67 (d, J=11.8 Hz, 1H).

Aufarbeitung

  1. additionA 250 mL round bottom flask was charged with a magnetic stir bar
  2. extractionextracted with EtOAc
  3. extractionThe combined organic extract
  4. washwas washed with brine
  5. dry with materialdried with MgSO4
  6. filtrationfiltered
  7. customconc., in vacuo to afford the crude material which
  8. customwas purified via silica gel chromatography (120 g)

Quellen und Nachweise

ORD-Eintrag
ord-3e78289d1b0541e69d93ecfe9082a68a
Quelldatensatz
uspto-grants-2016_06
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09371331B2

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