Triethylamine → (S)-tert-butyl 3-((8-chloro-3-cyanoisoquinolin-1-yl)amino)pyrrolidine-1-carboxylate

HRID 1476902Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1476902
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[Cl:12])[CH:5]=[C:4]([C:13]#[N:14])[N:3]=1.CCN(CC)CC.[NH2:22][C@H:23]1[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24]1>CN1C(=O)CCC1>[Cl:12][C:10]1[CH:9]=[CH:8][CH:7]=[C:6]2[C:11]=1[C:2]([NH:22][C@H:23]1[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24]1)=[N:3][C:4]([C:13]#[N:14])=[CH:5]2

Komponenten

5

Edukt 3

HCID 8471TriethylamineHCID 854071tert-butyl (3S)-3-aminopyrrolidine-1-carboxylateHCID 903870031,8-Dichloroisoquinoline-3-carbonitrile

Produkt 1

HCID 90387268(S)-tert-butyl 3-((8-chloro-3-cyanoisoquinolin-1-yl)amino)pyrrolidine-1-carboxylateAusbeute 89,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Reaktionsbedingungen

Temperatur
160 °C

Versuchsvorschrift

To a suspension of 1,8-dichloroisoquinoline-3-carbonitrile (0.3 g, 1.35 mmol) and Et3N (0.27 g, 2.7 mmol) in NMP (5 mL) was added (S)-tert-butyl 3-aminopyrrolidine-1-carboxylate (0.3 g, 1.62 mmol) at RT. The resulting mixture was stirred at 160° C. for 30 minutes in a microwave reactor. The reaction was subsequently quenched with water and the mixture was extracted with EtOAc (3×30 mL). The organic phase was dried over Na2SO4 and concentrated in vacuo. The crude product was purified by column chromatography eluting with ethyl acetate and petroleum ether (EtOAc/PE=1:10-1:2 gradient) on silica gel to give the title compound (0.45 g, 85%). 1H NMR (400 MHz, DMSO-d6) δ ppm 7.92-7.90 (d, J=8.0 Hz, 1H), 7.85-7.83 (m, 2H), 7.79-7.77 (d, J=8.0 Hz, 1H), 7.63 (s, 1H), 4.66-4.58 (m, 1H), 3.75-3.72 (t, J=8.0 Hz, 3H), 3.52-3.35 (m, 3H), 2.31-2.30 (br s, 1H), 2.11-2.07 (br s, 1H), 1.47-1.45 (s, 9H).

Aufarbeitung

  1. customThe reaction was subsequently quenched with water
  2. extractionthe mixture was extracted with EtOAc (3×30 mL)
  3. dry with materialThe organic phase was dried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by column chromatography
  6. washeluting with ethyl acetate and petroleum ether (EtOAc/PE=1:10-1:2 gradient) on silica gel

Quellen und Nachweise

ORD-Eintrag
ord-d284de297bba4334a29b30a411331f95
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09402841B2

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