Hydrochloric Acid → 1-(4-(4-fluorophenoxy)-2-methoxyphenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide

HRID 1473631Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1473631
C(P(C(C)(C)C)C1C(C)=C(C)C(C)=C(C)C=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.[F:35][C:36]1[CH:41]=[CH:40][C:39]([OH:42])=[CH:38][CH:37]=1.Cl[C:44]1[CH:49]=[CH:48][C:47]([C:50]2[C:59]3[C:54](=[CH:55][C:56]([S:60]([NH:63][C:64]4[CH:69]=[CH:68][N:67]=[CH:66][N:65]=4)(=[O:62])=[O:61])=[CH:57][CH:58]=3)[CH:53]=[CH:52][N:51]=2)=[C:46]([O:70][CH3:71])[CH:45]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Cl>O1CCOCC1>[F:35][C:36]1[CH:41]=[CH:40][C:39]([O:42][C:44]2[CH:49]=[CH:48][C:47]([C:50]3[C:59]4[C:54](=[CH:55][C:56]([S:60]([NH:63][C:64]5[CH:69]=[CH:68][N:67]=[CH:66][N:65]=5)(=[O:61])=[O:62])=[CH:57][CH:58]=4)[CH:53]=[CH:52][N:51]=3)=[C:46]([O:70][CH3:71])[CH:45]=2)=[CH:38][CH:37]=1

Komponenten

7

Edukt 5

HCID 313Hydrochloric AcidHCID 97324-FluorophenolHCID 62657Potassium Phosphate, TribasicHCID 11953610Di-tert-butyl[3,4,5,6-tetramethyl-2',4',6'-tris(propan-2-yl)-[1,1'-biphenyl]-2-yl]phosphaneHCID 866874841-(4-chloro-2-methoxyphenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide

Produkt 1

HCID 866877021-(4-(4-fluorophenoxy)-2-methoxyphenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamideAusbeute 22,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
135 °C

Versuchsvorschrift

A microwave vial charged with di-tert-butyl(2′,4′,6′-triisopropyl-3,4,5,6-tetramethyl-[1,1′-biphenyl]-2-yl)phosphine (0.017 g, 0.035 mmol), 4-fluorophenol (0.039 g, 0.351 mmol), 1-(4-chloro-2-methoxyphenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (0.075 g, 0.176 mmol), potassium phosphate (0.149 g, 0.703 mmol), 1.5 mL dioxane was heated to 135° C. in the microwave for 30 minutes. LC/MS showed mostly product, so the reaction mixture was filtered through a 0.45 μm syringe filter and was treated with HCl (4N in dioxane) (0.176 ml, 0.703 mmol). After stirring for 10 minutes, the reaction mixture was concentrated. Purification of the crude residue by reverse phase column chromatography [RediSep Gold C18, 10-100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)] gave 1-(4-(4-fluorophenoxy)-2-methoxyphenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (0.020 g, 0.040 mmol, 22.65% yield). 1H NMR (MeCN-d3) δ: 8.68 (d, J=5.7 Hz, 1H), 8.62 (s, 1H), 8.48 (s, 1H), 8.23 (d, J=8.5 Hz, 1H), 7.88-7.98 (m, 2H), 7.83 (d, J=9.0 Hz, 1H), 7.25-7.33 (m, 1H), 7.13-7.21 (m, 4H), 7.08 (d, J=5.4 Hz, 1H), 6.83 (s, 1H), 6.62-6.69 (m, 1H), 3.60 (s, 3H); (M+H)+=503.0.

Aufarbeitung

  1. filtrationso the reaction mixture was filtered through a 0.45 μm syringe
  2. filtrationfilter
  3. concentrationthe reaction mixture was concentrated
  4. customPurification of the crude residue by reverse phase column chromatography [RediSep Gold C18, 10-100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)]

Quellen und Nachweise

ORD-Eintrag
ord-2d93b91a732742379e78c48631e198ef
Quelldatensatz
uspto-grants-2015_04
Patentnummer
US09012443B2

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