2-Aminopyrimidine → n-(4-methoxybenzyl)pyrimidin-2-amine

To a mixture of 2-aminopyrimidine (104.7 g, 1.1 mol, 1 eq) and 4-methoxybenzaldehyde (150 g, 1.1 mol, 1 eq) in DCM (3 L), was added titanium(IV) chloride triisopropoxide (572 g, 2.2 mol, 2 eq). The reaction mixture was stirred at room temperature for 8 h. The reaction mixture was cooled to 0° C. and sodium triacetoxyborohydride (933 g, 4.4 mol, 4 eq) was added portionwise and stirred overnight at RT. After completion of reaction, the reaction mixture was cooled to 0° C., quenched with ice water and the solid was filtered through celite pad. The layers were separated and the aqueous layer extracted in DCM (1 L). The organic layer was dried over sodium sulfate and concentrated under reduced pressure to get the crude material which was purified by column chromatography (Silica [60-120 mesh]; eluted with 20-35% EtOAc in hexane) to yield 125 g (0.58 mol, 52% yield) of the title compound as a white solid. MS (ESI pos. ion) m/z: (M+2)+=216.2. 1H-NMR (400 MHz, DMSO-d6) δ 8.26 (d, J=3.68 Hz, 2H), 7.63 (t, J=6.16 Hz, 1H), 7.23 (d, J=8.48 Hz, 2H), 6.86 (d, J=8.56 Hz, 2H), 6.56-6.54 (m, 1H), 4.42 (d, J=6.32 Hz, 2H), 3.71 (s, 3H).

1. temperatureThe reaction mixture was cooled to 0° C.
2. stirringstirred overnight at RT
3. customAfter completion of reaction
4. temperaturethe reaction mixture was cooled to 0° C.
5. customquenched with ice water
6. filtrationthe solid was filtered through celite pad
7. customThe layers were separated
8. extractionthe aqueous layer extracted in DCM (1 L)
9. dry with materialThe organic layer was dried over sodium sulfate
10. concentrationconcentrated under reduced pressure
11. customto get the crude material which
12. customwas purified by column chromatography (Silica [60-120 mesh]; eluted with 20-35% EtOAc in hexane)

ORD record

ord-0c96032219f24877bec57a9b8a043fc9

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09212182B2