Potassium Carbonate → 8-Chloroisoquinolin-3-amine

HRID 40662Notes

Reaction equation

Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[Cl:12])[CH:5]=[C:4]([NH:13]C(=O)C)[N:3]=1.C(=O)([O-])[O-].[K+].[K+]>C(O)CCC.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:12][C:10]1[CH:9]=[CH:8][CH:7]=[C:6]2[C:11]=1[CH:2]=[N:3][C:4]([NH2:13])=[CH:5]2

Participants

Conditions

Temperature: 100 °C

Procedure

N-(1-Bromo-8-chloroisoquinolin-3-yl)acetamide (1.00 g, 3.33 mmol), potassium carbonate (0.508 mg, 3.67 mmol), triphenylphosphine (35 mg, 0.134 mmol) and palladium acetate (7.49 mg, 0.033 mmol) were stirred in 1-butanol (10 mL) with nitrogen bubbling through it for 10 minutes. Butanol (5 mL) was added to the reaction mixture, which was then heated overnight at 100° C. in a sealed vial. The reaction mixture was cooled, diluted with water and extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried (Na2SO4) and concentrated to give an orange solid. Flash chromatography on silica (20 g), eluting with 15-60% ethyl acetate-hexane, gave the title compound as a yellow solid (333 mg, 1.51 mmol, 45%). LC-MS (1) Rt=1.68 min; m/z (ES+) 221/223.

Workup

temperatureThe reaction mixture was cooled
extractionextracted twice with ethyl acetate
washThe combined organic layers were washed with brine
dry with materialdried (Na2SO4)
concentrationconcentrated
customto give an orange solid
washFlash chromatography on silica (20 g), eluting with 15-60% ethyl acetate-hexane

Sources & evidence

ORD record: ord-c80f3624e34f46f0a3b2f0a31e7d1f15
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08530468B2

Reaction notes

Loading…