Description
7-
Bromoisoquinoline is a synthetic intermediate useful for pharmaceutical synthesis.
Chemical Properties
Off-White Solid
Uses
7-Bromoisoquinoline (cas# 58794-09-5) is a compound useful in organic synthesis. It can be used for the preparation of estrone cortistatin analogs via Suzuki-Miyaura coupling. It could also be used for the preparation of pyrazolopyrimidinamine derivatives.
Preparation
The starting material 7-bromoisoquinoline was synthesised from 3-bromobenzaldehyde. According to
literature 7-bromoisoquinoline should be the major product.
Synthesis
General method: Aminoacetaldehyde dimethyl acetal (3.0 eq.) was added to a solution of m-bromobenzaldehyde (1.0 eq.) in toluene (30 mL). The reaction mixture was refluxed at 120°C (using a Dean-Stark device to remove water). After the feedstock was completely consumed, the reaction mixture was concentrated and the concentrate was redissolved. Concentrated H2SO4 (2 mL) and P2O5 (0.5 mL) were slowly added to the cooled concentrate. Subsequently, the reaction mixture was heated at 160 °C for 30 min, cooled to room temperature, neutralized with 10 M NaOH, extracted with EtOAc, and concentrated to dryness. The residue was purified by fast column chromatography (FCC) to afford 6-bromoisoquinoline (14b, 30 mg, 0.14 mmol, 14% yield) and 7-bromoisoquinoline (14c, 99 mg, 0.47 mmol, 22% yield) [20,21]. Ethyl chloroformate (1.0 eq.) was added dropwise to a DCM solution of isoquinoline 14b or 14c (1.0 eq.) at 0 °C, maintained at temperature and stirred for 30 min, followed by the addition of 2-trimethylsilylthiazole (1.0 eq.). The reaction mixture was stirred at room temperature for 3 hours, concentrated to dryness and the residue was purified by FCC. The purified product was dissolved in benzene (5 mL), o-chloroquinone (1.0 eq.) was added and the reaction mixture was refluxed for 5 hours. Upon completion of the reaction, it was diluted with 5% NaOH (10 mL), extracted by DCM and concentrated to dryness. The final product was purified by FCC to give the target compounds 9b and 9c.
References
[1] Molecules, 2017, vol. 22, # 8,
[2] ∗ J. B. M. R., Lucas, H., Smit, M. J., Noach, A. B. J., van Dinther, T. G., Rood, A. M. M., Jenneboer, A. J. S. M., & van Boeckel, C. A. A. (1999). Design, synthesis and testing of amino-bicycloaryl based orally bioavailable thrombin inhibitors. <i>Bioorganic &amp; Medicinal Chemistry Letters</i>, <i>9 19</i>, Pages 2837-2842.
https://doi.org/10.1016/S0960-894X(99)00483-7
