Hydrochloric Acid → (2-fluoro-3-nitro-phenyl)-(7H-pyrrolo[2,3-d]pyrimidin-5-yl)-methanol

Temperature

-5 °C

To 5-iodo-7H-pyrrolo[2,3-d]pyrimidine (35, 1.911 g, 7.799 mmol) 9.75 mL of tetrahydrofuran was added, the suspension was cooled to −5° C., and o-tolylmagnesium chloride (8.19 mL, 1.00 M in tetrahydrofuran, 8.19 mmol) was added. The reaction solution was stirred and kept between −5° C. and 0° C. for 30 minutes, then isopropylmagnesium chloride (4.29 mL, 2.0 M in tetrahydrofuran, 8.58 mmol) was slowly added dropwise. The reaction mixture was stirred and kept at 0° C. for 30 minutes, then 2-fluoro-3-nitro-benzaldehyde (36, 1.58 g, 9.36 mmol) in 4 mL of tetrahydrofuran was added dropwise using a syringe. The reaction mixture was stirred at −5° C. for 30 minutes and quenched with 1 N hydrochloric acid (1 equivalent) and extracted with ethyl acetate and saturated sodium bicarbonate in water. The organic layer was dried over magnesium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was purified by silica gel column chromatography eluting with a gradient of 60-80% ethyl acetate in hexanes (with 4% acetic acid). Appropriate fractions were combined and concentrated under vacuum to provide the desired compound (37, 699 mg). MS(ESI) [M+H+]+=289.4.

1. stirringThe reaction mixture was stirred
2. waitkept at 0° C. for 30 minutes
3. stirringThe reaction mixture was stirred at −5° C. for 30 minutes
4. extractionextracted with ethyl acetate and saturated sodium bicarbonate in water
5. dry with materialThe organic layer was dried over magnesium sulfate
6. filtrationfiltered
7. concentrationthe filtrate concentrated under vacuum
8. customThe resulting material was purified by silica gel column chromatography
9. washeluting with a gradient of 60-80% ethyl acetate in hexanes (with 4% acetic acid)
10. concentrationconcentrated under vacuum

ORD record

ord-6af772cb8ab64d5383ecb32c8b29a596

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08153641B2