Methyl 5-chloro-2,6-bis[(2,2-dimethylpropanoyl)amino]nicotinate → Methyl 2,6-Diamino-5-chloronicotinate

To a colorless solution of methyl 5-chloro-2,6-bis[(2,2-dimethylpropanoyl)amino]nicotinate (Example 2, Step 2, 153.9 g, 416 mmol) in methanol (1.5 L) was added a solution of potassium tert-butoxide (185 g, 1.65 mol) in methanol (500 mL) dropwise during the period of 20 min at room temperature under nitrogen atmosphere. Dissolving potassium tert-butoxide in methanol was exothermic, so potassium tert-butoxide must be added portionwise from powder addition funnel to methanol during the period of 2 h with ice-cold water bath. After the addition was completed, the reaction solution was stirred at reflux temperature for 1 h under nitrogen atmosphere, and cooled to room temperature. The resulting suspension was evaporated and ca. 1.3 L of methanol was removed (ca. 700 mL of methanol was remained). To this mixture was added water (1.2 L) and stirred at room temperature for 1 h with water bath (internal temperature was maintained at 20° C.), then the resulting suspension was filtered through paper filter and the pale yellow solid was dried under reduced pressure at 50° C. for 12 h to give 74.3 g (368.9 mmol, 89%) of the title compound as a pale yellow crystal.

1. additionAfter the addition
2. temperatureat reflux temperature for 1 h under nitrogen atmosphere
3. customThe resulting suspension was evaporated
4. customca. 1.3 L of methanol was removed (ca. 700 mL of methanol was remained)
5. additionTo this mixture was added water (1.2 L)
6. stirringstirred at room temperature for 1 h with water bath
7. temperature(internal temperature was maintained at 20° C.)
8. filtrationthe resulting suspension was filtered through paper
9. filtrationfilter
10. customthe pale yellow solid was dried under reduced pressure at 50° C. for 12 h

ORD record

ord-bbcc06e2cb684b1187425ba3c05f852f

Source dataset

uspto-grants-2005_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06951867B2