Cesium carbonate → (6-Methoxy-isoquinolin-3-yl)-(4-pyrrolidin-1-ylmethyl-pyridin-2-yl)-amine

HRID 1257120Notes

Reaction equation

HRID 1257120 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.[CH3:43][O:44][C:45]1[CH:46]=[C:47]2[C:52](=[CH:53][CH:54]=1)[CH:51]=[N:50][C:49]([NH2:55])=[CH:48]2.Cl[C:57]1[CH:62]=[C:61]([CH2:63][N:64]2[CH2:68][CH2:67][CH2:66][CH2:65]2)[CH:60]=[CH:59][N:58]=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>[CH3:43][O:44][C:45]1[CH:46]=[C:47]2[C:52](=[CH:53][CH:54]=1)[CH:51]=[N:50][C:49]([NH:55][C:59]1[CH:60]=[C:61]([CH2:63][N:64]3[CH2:65][CH2:66][CH2:67][CH2:68]3)[CH:62]=[CH:57][N:58]=1)=[CH:48]2

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 233211576-Methoxyisoquinolin-3-amineHCID 581138712-Chloro-4-(pyrrolidin-1-ylmethyl)pyridine

Product 1

HCID 44612348(6-Methoxy-isoquinolin-3-yl)-(4-pyrrolidin-1-ylmethyl-pyridin-2-yl)-amineYield 40%

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 6-methoxyisoquinolin-3-amine (195 mg, 1.12 mmol) (Preparation C-10), 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 (150 mg, 40% yield) as a yellow solid. 1H NMR (300 MHz, DMSO-d6): 8.84 (s, 1H), 8.27˜8.29 (m, 2H), 7.73 (d, J=8.7 Hz, 1 H), 7.60 (bs, 1H), 6.99˜7.08 (m, 3H), 7.02 (s, 1H), 6.86 (d, J=5.1 Hz, 1H), 3.94 (s, 3H), 3.62 (s, 2H), 2.58 (m, 4H), 1.83 (m, 4H); MS: m/z 335.2 (M+H+).

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-3ab79e0739224c7591c18a39dc1a4aae
Source dataset
uspto-grants-2013_06
Patent number
US08461339B2

Reaction notes

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