Potassium Carbonate → 7-bromo-N-methylisoquinolin-3-amine

HRID 880996Notes

Reaction equation

[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7](Cl)[N:8]=[CH:9]2)=[CH:4][CH:3]=1.Cl.[CH3:14][NH2:15].C(=O)([O-])[O-].[K+].[K+]>COCCOCCOC.O>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH:15][CH3:14])[N:8]=[CH:9]2)=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 150 °C

Procedure

A mixture of 7-bromo-3-chloroisoquinoline (100 mg, 0.4 mmol), methylamine hydrochloride (139 mg, 2.06 mmol), and potassium carbonate (456 mg, 3.30 mmol) in 1-methoxy-2-(2-methoxyethoxyl)ethane (1 mL) was heated to 150° C. and stirred for 60 hours. Additional methylamine hydrochloride (100 mg, 1.5 mmol) and potassium carbonate (200 mg, 1.4 mmol) were added and heating was continued for another 40 hours. The reaction was cooled to room temperature and diluted with water. The mixture was stirred for 30 minutes. The resulting solid was filtered off, rinsed with water and dried under vacuum. Purification by flash column chromatography (10-30% ethyl acetate/heptanes) gave the title compound (82 mg) as a pale yellow solid. −APCI (M−H+1) 237.8; 1H NMR (400 MHz, CDCl3, δ): 8.70 (s, 1H), 7.84 (d, J=1.95 Hz, 1H), 7.48 (dd, J=8.97, 2.15 Hz, 1H), 7.38 (d, J=8.97 Hz, 1H), 6.39 (s, 1H), 2.92 (s, 3H).

Workup

temperatureheating
waitwas continued for another 40 hours
temperatureThe reaction was cooled to room temperature
stirringThe mixture was stirred for 30 minutes
filtrationThe resulting solid was filtered off
washrinsed with water
customdried under vacuum
customPurification by flash column chromatography (10-30% ethyl acetate/heptanes)

Sources & evidence

ORD record: ord-ac6d22ffd72043a0a3e25f0aa28a3f77
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08993586B2

Reaction notes

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