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

HRID 1257119

Reaktionsgleichung

Reaktionsgleichung von HRID 1257119
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.[Cl: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>[Cl: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 233211687-Chloroisoquinolin-3-amineHCID 581138712-Chloro-4-(pyrrolidin-1-ylmethyl)pyridine

Produkt 1

HCID 445962937-Chloro-N-(4-(pyrrolidin-1-ylmethyl)pyridin-2-yl)isoquinolin-3-amineAusbeute 32 %

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-chloroisoquinolin-3-amine (200 mg, 1.12 mmol) (Preparation C-9), 2-chloro-4-pyrrolidin-1-ylmethyl-pyridine (220 mmg, 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 (120 mg, 32% yield) as a yellow solid.

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-cb67fe8c1d0546d99d6ff28907c2e0d8
Quelldatensatz
uspto-grants-2013_06
Patentnummer
US08461339B2

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