Ammonia → 5-Iodo-6-methylpyrimidine-2,4-diamine

Temperature

0 °C

To a 100 mL steel pressure vessel was added 2-amino-4-chloro-6-methylpyrimidine (4.00 g, 28.00 mmol). A saturated solution of NH3 in MeOH (40 mL) was added and the vessel sealed. The pressure vessel was placed into a 160° C. oil bath and heated for 15 h. The vessel was cooled to 0° C. and opened and the solvent removed to give the crude diaminopyrimidine (4.4 g) as the HCl salt. The crude salt was dissolved in MeOH (82.5 mL), and ICl (82.5 mL) was added dropwise over 50 min. The reaction was stirred at 25° C. for 14 h and the solvent removed. The viscous oil was stirred in Et2O (300 mL) for 30 min. The resulting solid was filtered and washed with Et2O (3×20 mL) to give the crude iodinated pyrimidine as a yellow solid (10.1 g). The solids were suspended in 1, 0 N NaOH (300 mL) and stirred at 25° C. for 2 h. The solids were filtered, washed with water (2×20 mL), and allowed to dry to afford 2,4-Diamino-5-iodo-6-methylpyrimidine as a white powder (5.6 g, 80%). An analytical sample was prepared by recrystallization from MeCN to give 2,4-Diamino-5-iodo-6-methylpyrimidine as colorless crystals: Rf=0.25 (9:1, CHCl3:MeOH); mp=154-156° C.; 1H NMR (DMSO-d6) δ 6.38 (s, 2H), 6.09 (s, 2H), 2.24 (s, 3H); 13C NMR (DMSO-d6) δ 166.7, 163.0, 162.3, 63.8, 28.4; HREI[M+]249.9715 (calculated C5H7IN4: 249.9715); Anal. (C5H7IN4) C, H, N.

1. customthe vessel sealed
2. customwas placed into a 160° C.
3. temperatureheated for 15 h
4. customthe solvent removed
5. customto give the crude diaminopyrimidine (4.4 g) as the HCl salt
6. customthe solvent removed
7. stirringThe viscous oil was stirred in Et2O (300 mL) for 30 min
8. filtrationThe resulting solid was filtered
9. washwashed with Et2O (3×20 mL)
10. customto give the crude iodinated pyrimidine as a yellow solid (10.1 g)
11. stirringstirred at 25° C. for 2 h
12. filtrationThe solids were filtered
13. washwashed with water (2×20 mL)
14. customto dry

ORD record

ord-495772796d99458cabc28568a990b15c

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08426432B2