Dimethyl Sulfide → HCID 66932650, compound

To a stirred solution of 3-(1H-pyrrolo[2,3-b]pyridin-3-yl)alanine monohydrate (10.0 g, 50.0 mmol) in THF (140 mL) at 0° C. was slowly added BF3.Et2O complex (7.0 mL, 60.0 mmol) followed by BH3.Me2S complex (10M in THF, 14.5 mL, 145.0 mmol). The reaction mixture was stirred at r.t. for 16 h and on completion the excess borane was quenched by the addition of MeOH (5 mL) at 0° C. The reaction mixture was concentrated, dissolved in EtOAc (120 mL) and washed with aqueous 20% NaOH solution (2×60 mL). The organic layer was then extracted into aqueous 2M HCl (2×150 mL). The combined acidic aqueous layers were then basified to pH 14 (addition of solid NaOH) and re-extracted with EtOAc (2×100 mL). The combined organic fractions were then dried over MgSO4, filtered and concentrated in vacuo to give the title compound as a white solid (4.9 g, 52%). δH (MeOD-d3) 12.13 (1H, br. s), 8.97 (1H, dd, J 4.7 and 1.5 Hz), 8.06 (1H, s), 7.82 (1H, m), 4.12 (1H, dd, J 10.3 and 4.9 Hz), 4.01 (1H, dd, J 10.3 and 6.5 Hz), 3.75 (1H, m), 3.59 (1H, dd, J 14.0 and 5.5 Hz), 3.37 (1H, dd, J 14.0 and 7.3 Hz). Exchangeable protons were not observed.

1. customat 0° C.
2. customwas quenched by the addition of MeOH (5 mL) at 0° C
3. concentrationThe reaction mixture was concentrated
4. dissolutiondissolved in EtOAc (120 mL)
5. washwashed with aqueous 20% NaOH solution (2×60 mL)
6. extractionThe organic layer was then extracted into aqueous 2M HCl (2×150 mL)
7. additionThe combined acidic aqueous layers were then basified to pH 14 (addition of solid NaOH)
8. extractionre-extracted with EtOAc (2×100 mL)
9. dry with materialThe combined organic fractions were then dried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated in vacuo

ORD record

ord-c22a8fc97489485d8ac5f0058ea82f7b

Source dataset

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07888344B2