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

HRID 537186Notes

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-methoxyethoxy)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-939eb691bb9d48fd9c50db957ced2f53
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08859773B2

Reaction notes

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