Formic Acid → HCID 178432644, compound

Temperature

55 °C

5-Bromo-6-methylpicolinamide (1 g, 4.65 mmol) and N,N-dimethylformamide dimethylacetal (20 mL) were combined in a 100 mL round-bottom flask with a stir bar and heated at 85° C. under a reflux condenser under nitrogen for 3 h. The resulting mixture was concentrated under reduced pressure and dried under vacuum to give yellow oil, which was used in the next step without purification. The residue was diluted with acetic acid (10 mL) and hydrazine (2.5 mL, 70.3 mmol) was added drop-wise and allowed to stir at room temperature for 5 h. The reaction mixture was poured into ice water. The resulting solid was filtered, washed with water and dried to give the desired product as a white solid. The aqueous filtrate was extracted with dichloromethane. The organic layer was concentrated under reduced pressure nearly to dryness to yield additional material. Combination of two batches gave the desired product (0.7 g, 2.9 mmol, 63% yield). MS (ESI) m/z 241.1 [M+2]+. Alternate approach: 5-Bromo-6-methylpicolinonitrile (1 equiv) and hydrazine monohydrate (2.0 equiv) were combined in absolute ethanol (4×vol) and heated to 55° C. for 24 h. The slurry was cooled to room temperature and filtered. The collected solids were washed with ethanol and methyl tent-butyl ether, and the solids were dried to deliver 5-bromo-6-methylpicolinimidohydrazide as a beige powder. 5-Bromo-6-methylpicolinimidohydrazide and formic acid (15 equiv) were combined and heated to 100° C. with stirring for 6 h. The reaction solution was cooled to 40° C., treated with methanol, stirred for 30 min and concentrated under reduced pressure to 20% of the reaction volume. The mixture was diluted with methanol and again concentrated under reduced pressure to 20% of the reaction volume. The resulting solids were filtered, washed with water, and dried to give the title compound as an off-white powder.

1. temperatureThe slurry was cooled to room temperature
2. filtrationfiltered
3. washThe collected solids were washed with ethanol and methyl tent-butyl ether
4. customthe solids were dried
5. temperatureheated to 100° C.
6. temperatureThe reaction solution was cooled to 40° C.
7. stirringstirred for 30 min
8. concentrationconcentrated under reduced pressure to 20% of the reaction volume
9. additionThe mixture was diluted with methanol
10. concentrationagain concentrated under reduced pressure to 20% of the reaction volume
11. filtrationThe resulting solids were filtered
12. washwashed with water
13. customdried

ORD record

ord-5f179f78c42e4f169838f32cc50496b1

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08569494B2