5-broMo-4-chloro-7-Methyl-7H-pyrrolo[2,3-d]pyriMidine

Chemical Properties

5-broMo-4-chloro-7-Methyl-7H-pyrrolo[2,3-d]pyriMidine is Light Brown Solid

Uses

5-broMo-4-chloro-7-Methyl-7H-pyrrolo[2,3-d]pyriMidine is used in the preparation of indoline derivatives as PERK inhibitors.

Synthesis

Example 1 Synthesis of 5-(1H-1,3-benzodiazol-2-yl)-7-methyl-N-phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine Step 1: Preparation of 5-bromo-4-chloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine. To a stirred solution of 4-chloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (6.02 g, 35.9 mmol) in dichloromethane (120 mL) at 0 °C was added N-bromosuccinimide (7.67 g, 43.1 mmol). The reaction mixture was stirred at room temperature for 2 hours. Upon completion of the reaction, the reaction was quenched with saturated aqueous sodium bicarbonate solution (200 mL) and extracted with dichloromethane (200 mL). The organic layers were combined, dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane/ethyl acetate=10/1) to afford 5-bromo-4-chloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (8.27 g, 93% yield) as a white solid.LCMS (Method A) m/z: [M+1]+ 247.9; retention time tR=2.70 min.

References

[1] Journal of Medicinal Chemistry, 2012, vol. 55, # 16, p. 7193 - 7207
[2] Patent: WO2011/18894, 2011, A1. Location in patent: Page/Page column 25-26
[3] Patent: WO2018/194885, 2018, A1. Location in patent: Page/Page column 16
[4] Patent: WO2011/119663, 2011, A1. Location in patent: Page/Page column 82
[5] MedChemComm, 2014, vol. 5, # 10, p. 1500 - 1506