Triethylamine → 1-(2,2-difluorobenzo-[d][1,3]dioxol-5-yl)-N-(1-(6-oxo-1,6-dihydropyridin-3-yl)isoquinolin-3-yl)cyclopropane-carboxamide

HRID 1471849

Reaktionsgleichung

Reaktionsgleichung von HRID 1471849
[F:1][C:2]1([F:35])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3([C:14]([NH:16][C:17]4[N:18]=[C:19]([C:27]5[CH:28]=[N:29][C:30]([O:33]C)=[CH:31][CH:32]=5)[C:20]5[C:25]([CH:26]=4)=[CH:24][CH:23]=[CH:22][CH:21]=5)=[O:15])[CH2:13][CH2:12]3)=[CH:10][C:4]=2[O:3]1.C(N(CC)CC)C>O1CCOCC1.Cl>[F:35][C:2]1([F:1])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3([C:14]([NH:16][C:17]4[N:18]=[C:19]([C:27]5[CH:32]=[CH:31][C:30](=[O:33])[NH:29][CH:28]=5)[C:20]5[C:25]([CH:26]=4)=[CH:24][CH:23]=[CH:22][CH:21]=5)=[O:15])[CH2:13][CH2:12]3)=[CH:10][C:4]=2[O:3]1

Komponenten

5

Edukt 2

HCID 8471TriethylamineHCID 577330101-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)-N-(1-(6-methoxypyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide

Produkt 1

HCID 577330241-(2,2-difluorobenzo-[d][1,3]dioxol-5-yl)-N-(1-(6-oxo-1,6-dihydropyridin-3-yl)isoquinolin-3-yl)cyclopropane-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 313Hydrochloric AcidLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

1-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)-N-(1-(6-methoxypyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide (100 mg, 0.210 mmol) was dissolved in a mixture of 1.2 mL of 1,4-dioxane and 0.6 mL of 4M aqueous hydrochloric acid. The solution was heated at 90° C. for 2 hours. The crude reaction mixture was quenched with one equivalent of triethylamine and was then evaporated to dryness. The crude product was partitioned between dichloromethane and water. The organic layer was separated, dried over sodium sulfate, and a portion of the material was purified on 12 g of silica gel utilizing a gradient of 0-10% methanol in dichloromethane to yield 1-(2,2-difluorobenzo-[d][1,3]dioxol-5-yl)-N-(1-(6-oxo-1,6-dihydropyridin-3-yl)isoquinolin-3-yl)cyclopropane-carboxamide as a white solid. ESI-MS m/z calc. 461.1. found 461.9 (M+1)+. Retention time 1.67 minutes.

Aufarbeitung

  1. customThe crude reaction mixture
  2. customwas then evaporated to dryness
  3. customThe crude product was partitioned between dichloromethane and water
  4. customThe organic layer was separated
  5. dry with materialdried over sodium sulfate
  6. customa portion of the material was purified on 12 g of silica gel utilizing a gradient of 0-10% methanol in dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-20b92abfb0c04ae982998a37ad4cd938
Quelldatensatz
uspto-grants-2015_04
Patentnummer
US09012473B2

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