N-bromobutanimide → 2-Bromo-3-[5-(2,2-dimethyl-propionylamino)-pyrazin-2-yl]-3-oxo-propionic acid tert-butyl ester

A 1-L round bottomed flask equipped with a magnetic stirrer was charged with 73.00 mg (0.841 mmol) of lithium bromide and the butanone solution obtained in step 3 (ca. 100 mL), which theoretically contained 27.09 g (84.30 mmol) of 3-[5-(2,2-dimethyl-propionylamino)-pyrazin-2-yl]-3-oxo-propionic acid-tert-butyl ester and ca. 73 mL of butanone. To the resulting mixture was added a total of 15.16 g (85.17 mmol) of N-bromosuccinimide portionwise with careful reaction monitoring by HPLC. After stirring at room temperature for 1 h, HPLC analysis indicated complete reaction. The reaction mixture was concentrated at 25° C./25 mmHg to a volume of ca. 70 mL, then diluted with 130 mL of ethyl acetate and washed with 3×100 mL L of water. After concentration at 35° C./60 mmHg to a volume of ca. 90 mL, the resulting suspension was diluted with 200 mL of heptane, and re-concentrated to a volume of ca. 90 mL. Then, 200 mL of heptane was added, and the suspension was again concentrated to a volume of ca, 150 mL. The solid was then collected by filtration, washed with 2×50 mL of heptane and dried by suction to give 32.16 g of the title compound as a light yellow solid; 98.7% pure as determined by HPLC analysis (HPLC column Zorbax XDB-C8, 3×100 mm, 3.5 μm, eluent 20-100% acetonitrile/water+01. % TFA over 10 min at 0.5 mL/min, detection at UV 254 nm, retention time 9.52 min).

1. customA 1-L round bottomed flask equipped with a magnetic stirrer
2. customreaction
3. concentrationThe reaction mixture was concentrated at 25° C./25 mmHg to a volume of ca. 70 mL
4. additiondiluted with 130 mL of ethyl acetate
5. washwashed with 3×100 mL L of water
6. concentrationAfter concentration at 35° C./60 mmHg to a volume of ca. 90 mL
7. additionthe resulting suspension was diluted with 200 mL of heptane
8. concentrationre-concentrated to a volume of ca. 90 mL
9. additionThen, 200 mL of heptane was added
10. concentrationthe suspension was again concentrated to a volume of ca, 150 mL
11. filtrationThe solid was then collected by filtration
12. washwashed with 2×50 mL of heptane
13. customdried by suction

ORD record

ord-d44c0ab013454a00a29d89cf16f093fb

Source dataset

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07727750B2