3-(3-Fluorophenyl)piperidine--hydrogen chloride (1/1) → HCID 86687677, Verbindung

HRID 1473612Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1473612
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([S:12]([NH:15][C:16]3[CH:21]=[CH:20][N:19]=[CH:18][N:17]=3)(=[O:14])=[O:13])=[CH:9][CH:10]=2)[CH:5]=[CH:4][N:3]=1.[Cl-].C(C1C=CC=C(CCC)C=1[N+]1C=CN(C2C(CCC)=CC=CC=2CCC)C=1)CC.Cl.[F:53][C:54]1[CH:55]=[C:56]([CH:60]2[CH2:65][CH2:64][CH2:63][NH:62][CH2:61]2)[CH:57]=[CH:58][CH:59]=1.CC(C)([O-])C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[F:53][C:54]1[CH:55]=[C:56]([CH:60]2[CH2:65][CH2:64][CH2:63][N:62]([C:2]3[C:11]4[C:6](=[CH:7][C:8]([S:12]([NH:15][C:16]5[CH:21]=[CH:20][N:19]=[CH:18][N:17]=5)(=[O:14])=[O:13])=[CH:9][CH:10]=4)[CH:5]=[CH:4][N:3]=3)[CH2:61]2)[CH:57]=[CH:58][CH:59]=1

Komponenten

7

Edukt 4

HCID 190956263-(3-Fluorophenyl)piperidine--hydrogen chloride (1/1)HCID 223147471,3-Bis(2,6-di-1-propylphenyl)imidazolium chlorideHCID 23676156Sodium t-butoxideHCID 866876591-chloro-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide

Produkt 1

HCID 86687677HCID 86687677, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
130 °C

Versuchsvorschrift

A vial was charged with 1-chloro-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (Intermediate GG; 0.200 g, 0.624 mmol), Pd2(dba)3 (0.029 g, 0.031 mmol), 1,3-bis(2,6-di-1-propylphenyl)imidazolium chloride (0.027 g, 0.062 mmol), 3-(3-fluorophenyl)piperidine hydrochloride (0.202 g, 0.935 mmol) and sodium tert-butoxide (0.240 g, 2.494 mmol). Dioxane (6.24 ml) was added and the reaction was flushed with argon and stirred at 130° C. for one hour. The reaction was diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were dried with sodium sulfate, filtered, and concentrated. The material was purified via column chromatography (RediSep Gold 40 g, gradient elution 0-10% MeOH:DCM) to afford 1-(3-(3-fluorophenyl)piperidin-1-yl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ=8.57 (s, 1H), 8.48 (s, 1H), 8.29-8.25 (m, 1H), 8.23 (d, J=9.0 Hz, 1H), 8.19 (d, J=5.7 Hz, 1H), 7.95 (dd, J=1.8, 8.9 Hz, 1H), 7.57 (d, J=5.8 Hz, 1H), 7.35 (dt, J=6.5, 8.0 Hz, 1H), 7.25-7.16 (m, 2H), 7.08-6.97 (m, 2H), 3.79 (t, J=13.0 Hz, 2H), 3.21-3.10 (m, 1H), 3.08-2.91 (m, 2H), 2.09-1.99 (m, 1H), 1.97-1.83 (m, 2H), 1.79-1.65 (m, 1H). m/z (ESI) 464.2 (M+H)+.

Aufarbeitung

  1. customthe reaction was flushed with argon
  2. additionThe reaction was diluted with ethyl acetate
  3. washwashed with water
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. dry with materialthe combined organic layers were dried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe material was purified via column chromatography (RediSep Gold 40 g, gradient elution 0-10% MeOH:DCM)

Quellen und Nachweise

ORD-Eintrag
ord-35caf521c8b94c709aac56e0a30a2de3
Quelldatensatz
uspto-grants-2015_04
Patentnummer
US09012443B2

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