Methylamine → 4,6-Dichloro-n-methylpyrimidin-2-amine

Methylamine (2M solution, 113 mL, 217 mmol, 2.05 equiv) was charged to a 1 L 3-neck flask fitted with a magnetic stirrer and a thermometer. The mixture was chilled in an ice bath. To this stirred solution was added via addition funnel a solution of 4,6-dichloro-2-(methylsulfonyl)pyrimidine (25 g, 110 mmol) in EtOAc (250 mL) portionwise over a 25 minutes period. The temp was between 5-10° C. After completion of addition, the ice bath was removed, and the mixture was stirred for 1 hour at ambient temperature. LCMS showed conversion complete. The suspension was filtered, and washed with EtOAc. The filtrate was concentrated in vacuo. The residue was partitioned between water (100 mL) and EtOAc (450 mL). The organic was washed with brine, dried over MgSO4, filtered and concentrated in vacuo to give white solids, which were triturated in 150 mL of CH2Cl2. These solids were collected by filtration and washing with cold CH2Cl2 (50 mL). Drying under house vacuum at room temperature for 20 hours, and then high vacuum at room temperature for 3 hours gave 9.31 g of the title compound as a solid. LC-MS (ES) m/z=179 [M+H]+.

1. customfitted with a magnetic stirrer
2. temperatureThe mixture was chilled in an ice bath
3. customwas between 5-10° C
4. additionAfter completion of addition
5. customthe ice bath was removed
6. filtrationThe suspension was filtered
7. washwashed with EtOAc
8. concentrationThe filtrate was concentrated in vacuo
9. customThe residue was partitioned between water (100 mL) and EtOAc (450 mL)
10. washThe organic was washed with brine
11. dry with materialdried over MgSO4
12. filtrationfiltered
13. concentrationconcentrated in vacuo
14. customto give white solids, which
15. customwere triturated in 150 mL of CH2Cl2
16. filtrationThese solids were collected by filtration
17. washwashing with cold CH2Cl2 (50 mL)
18. customDrying under house vacuum at room temperature for 20 hours

ORD record

ord-44e295ba6c2e4a1cbd5f8d03cfd46065

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08697685B2