4-Chloro-5-azaindole

Uses

4-Chloro-1H-pyrrolo[3,2-c]pyridine is an intermediate used in the synthetic preparation of potent gp120-CD4 inhibitors.

Uses

4-CHLORO-5-AZAINDOLE is an intermediate used in the synthetic preparation of potent gp120-CD4 inhibitors.

Synthesis

General procedure for the synthesis of 4-chloropyrrolo[3,2-c]pyridine from 4-chloro-2,3-dihydro-1H-pyrrolo[3,2-c]pyridine: 1. Synthesis of the intermediate 13-bromo-4-chloro-1H-pyrrolo[3,2-c]pyridine: To a solution of 4-chloro-2,3-dihydro-1H-pyrrolo[3,2-c]pyridine (2.18 g, 14.2 mmol) in tetrahydrofuran (THF, 60 mL) was added manganese dioxide (MnO2, 7 g, 80.5 mmol) and the mixture was heated to reflux. After 5 hours of reaction, manganese dioxide (3 g, 34.5 mmol) was added and stirring was continued overnight. After completion of the reaction, the mixture was filtered through diatomaceous earth and the filtrate was concentrated to give a white solid product (1.95 g, 91% yield). 2. The indole derivative (1.48 g, 9.72 mmol) obtained above was dissolved in dichloromethane (CH2Cl2, 50 mL) and cooled to 0 °C under nitrogen protection. N-bromosuccinimide (NBS, 1.82 g, 10.2 mmol) was added slowly and the reaction was carried out for 30 min, then the ice bath was removed and stirring was continued for 30 min. After completion of the reaction, the target bromide (1.53 g, 68% yield) was filtered and dried under high vacuum. The product was detected by mass spectrometry (ES+), m/e = 231; 1H NMR (DMSO) δ 7.48 (1H, d), 7.80 (1H, s), 8.00 (1H, d).

References

[1] Patent: WO2007/95223, 2007, A2. Location in patent: Page/Page column 41