Cesium carbonate → 7-Fluoro-N-(4-(pyrrolidin-1-ylmethyl)pyridin-2-yl)isoquinolin-3-amine

HRID 1257121

Reaktionsgleichung

Reaktionsgleichung von HRID 1257121
CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[F:43][C:44]1[CH:53]=[C:52]2[C:47]([CH:48]=[C:49]([NH2:54])[N:50]=[CH:51]2)=[CH:46][CH:45]=1.Cl[C:56]1[CH:61]=[C:60]([CH2:62][N:63]2[CH2:67][CH2:66][CH2:65][CH2:64]2)[CH:59]=[CH:58][N:57]=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1COCC1>[F:43][C:44]1[CH:53]=[C:52]2[C:47]([CH:48]=[C:49]([NH:54][C:58]3[CH:59]=[C:60]([CH2:62][N:63]4[CH2:64][CH2:65][CH2:66][CH2:67]4)[CH:61]=[CH:56][N:57]=3)[N:50]=[CH:51]2)=[CH:46][CH:45]=1

Komponenten

8

Edukt 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 233211407-Fluoroisoquinolin-3-amineHCID 581138712-Chloro-4-(pyrrolidin-1-ylmethyl)pyridine

Produkt 1

HCID 446123517-Fluoro-N-(4-(pyrrolidin-1-ylmethyl)pyridin-2-yl)isoquinolin-3-amineAusbeute 31,9 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 1140TolueneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

Pd2(dba)3(102 mmg, 0.11 mmol) and xantphos (92 mg, 0.16 mmol) were added to a solution of 7-fluoroisoquinolin-3-amine (182 mg, 1.12 mmol) (Preparation C-11), 2-chloro-4-pyrrolidin-1-ylmethyl-pyridine (220 mg, 1.12 mmol) (Preparation B-11) and Cs2CO3 (500 mg, 1.53 mmol) in toluene (50 mL). The suspension was heated under reflux overnight, and THF (50 mL) was added in to dilute the mixture. After filtration, the filtrate was concentrated. The crude material was further purified by silica gel chromatography (EtOAc/Hexane=1/1) and afforded the title compound (115 mg, 31.8% yield) as a yellow solid. 1H NMR (300 MHz, DMSO-d6): 8.94 (s, 1H), 8.42 (s, 1H), 8.27 (d, J=5.4 Hz, 1H), 7.72˜7.77 (m, 2H), 7.33˜7.46 (m, 2H), 7.02 (s, 1H), 6.84 (d, J=5.4 Hz, 1H), 3.59 (s, 2H), 2.55 (m, 4H), 1.81 (m, 4H); MS: m/z 323.1 (M+H+).

Aufarbeitung

  1. temperatureThe suspension was heated
  2. temperatureunder reflux overnight
  3. additionto dilute the mixture
  4. filtrationAfter filtration
  5. concentrationthe filtrate was concentrated
  6. customThe crude material was further purified by silica gel chromatography (EtOAc/Hexane=1/1)

Quellen und Nachweise

ORD-Eintrag
ord-8a4a168741c148e89a40389d45557415
Quelldatensatz
uspto-grants-2013_06
Patentnummer
US08461339B2

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