HCID 58166476, compound → HCID 178484257, compound

Zinc chloride (1.24 g, 9.12 mmol) was added to a mixture of the formamidine product from Step 2 (0.656 g, 2.28 mmol) in absolute EtOH (10 mL). The resultant mixture was heated to reflux under N2. The mixture gradually turned into a light yellow, homogeneous solution. After refluxing for 90 min a precipitate had formed, and after 2 h, the reaction mixture was allowed to cool to room temperature and was concentrated in vacuo. The residue was treated with CH2Cl2 (75 mL, slightly turbid in appearance) and washed with H2O (25 mL). As soon as H2O was added a white precipitate formed in both layers in the separatory funnel. The solid was removed by vacuum filtration. The solid was washed with H2O followed by Et2O. After air-drying overnight the white solid (0.58 g) was treated with 1:1 CH2Cl2/MeOH (˜70 mL) and heated to reflux (turbid mixture). The mixture was filtered and the filtrate was concentrated in vacuo. The residual solid was slurried with hexanes/Et2O (˜3:1) and isolated by vacuum filtration, air-dried and then vacuum oven dried (70-80° C.) to give N′-(5-fluoro-2-hydroxypyrimidin-4-yl)-N,N-dimethylformamidine (0.417 g, 78%) as a white powder: mp 291-293° C. dec; 1H NMR (300 MHz, DMSO-d6) δ 8.03 (d, J=6.9 Hz, 1H), 7.62 (br s, 1H), 7.40 (br s, 1H), 7.17 (d, J=7.8 Hz, 2H), 7.12 (d, J=8.1 Hz, 2H), 4.73 (s, 2H), 2.25 (s, 3H); 13C NMR (150 MHz, DMSO-d6) δ 158.2, 154.8, 137.3, 136.3 (d, J=240 Hz), 135.3, 131.1 (d, J=30.6 Hz), 129.7, 128.3, 51.8, 21.3; ESIMS m/z 234 ([M+H]+), m/z 232 ([M−H]−); IR 3298 (m, br), 3100 (m, br), 1685 (s), 1619 (s), 1518 (s), 1447 (m), 1383 (m), 1343 (w), 1120 (w), 776 (w) cm−1.

1. temperatureto reflux under N2
2. temperatureAfter refluxing for 90 min a precipitate
3. customhad formed
4. concentrationwas concentrated in vacuo
5. additionThe residue was treated with CH2Cl2 (75 mL, slightly turbid in appearance) and
6. washwashed with H2O (25 mL)
7. additionAs soon as H2O was added a white precipitate
8. customformed in both layers in the separatory funnel
9. customThe solid was removed by vacuum filtration
10. washThe solid was washed with H2O
11. dry with materialAfter air-drying overnight the white solid (0.58 g)
12. additionwas treated with 1:1 CH2Cl2/MeOH (˜70 mL)
13. temperatureheated
14. temperatureto reflux (turbid mixture)
15. filtrationThe mixture was filtered
16. concentrationthe filtrate was concentrated in vacuo
17. customisolated by vacuum filtration
18. customair-dried
19. customvacuum oven dried (70-80° C.)

ORD record

ord-15aa79ebe47f44da99ab80c3f67cc2cd

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08916579B2