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

HRID 1257119

Reaction equation

HRID 1257119 reaction equation
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

Participants

8

Reactant 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

Product 1

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

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-cb67fe8c1d0546d99d6ff28907c2e0d8
Source dataset
uspto-grants-2013_06
Patent number
US08461339B2

Linked notes

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