4-Methoxybenzylamine → 1-[6-(4-Methoxy-benzylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]-ethanone

Temperature

65 °C

The reaction was performed according to the protocol described in Org. Lett., 2010, 12(20), 4438-4441. A vial containing 1-(6-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-ethanone (100 mg, 0.49 mmol), BrettPhos (2.62 mg, 4.88 μmol) and BrettPhos precatalyst (3.9 mg, 4.88 μmol) and a magnetic stir bar was sealed with a teflon screw-cap, evacuated and backfilled with argon. A balloon of argon was placed on top of the vial, to allow a pressure balance and LiHMDS (1 M in THF, 1172 μL, 1.17 mmol) was added, followed by 4-methoxybenzylamine (76 μL, 0.59 mmol). The reaction mixture was stirred and heated at 65° C. for 22 h, then allowed to cool to RT, quenched by the addition of 1 M HCl (1 mL) diluted with EtOAc and poured into a saturated aqueous solution of NaHCO3. After extracting twice with EtOAc, the combined organic layers were washed with brine, dried (Na2SO4), filtered and concentrated. The crude was purified by flash column chromatography on silica gel (c-hexane to EtOAc). TLC, Rf (EtOAc)=0.75; MS (UPLC/MS): 296.2 [M+H]+, 591.3 [2M+H]+, 613.2 [2M+Na]+; tR (HPLC conditions f): 1.5 min.

1. customscrew-cap
2. customevacuated
3. additionwas added
4. temperatureto cool to RT
5. customquenched by the addition of 1 M HCl (1 mL)
6. additiondiluted with EtOAc
7. additionpoured into a saturated aqueous solution of NaHCO3
8. extractionAfter extracting twice with EtOAc
9. washthe combined organic layers were washed with brine
10. dry with materialdried (Na2SO4)
11. filtrationfiltered
12. concentrationconcentrated
13. customThe crude was purified by flash column chromatography on silica gel (c-hexane to EtOAc)
14. custom1.5 min.

ORD record

ord-c4ea305c38b34699a189b969a4b8a0b8

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09085555B2