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1H NMR (500 MHz, CDCl3) δ = 1.85 (s, 2H), 2.39 (s, 2H), 2.56 (s, 2H), 4.05 (m, 4H), 4.81 (d, J = 25.02 Hz, 2H), 6.76 (s, 1H), 6.93 (s, 1H).
13C NMR (125 MHz, CDCl3) δ = 24.7, 27.5, 31.9, 37.9, 42.2, 43.3, 105.2, 117.8, 124.6, 145.4, 147.7, 149.9, 150.8, 154.6, 156.9, 171.3.
Compound Name:
1,3-dichloro-2-fluorobenzene
Molecular Formula: C6H3Cl2F
Molecular Weight: 165.0
CAS Registry No.:
2268-05-5
1H NMR CDCL3
399.65 MHz | |
C6 H3 Cl2 F | 0.040 g : 0.5 ml CDCl3 |
1,3-dichloro-2-fluorobenzene |
Hz ppm Int.
2926.51 7.323 808 2919.92 7.307 846 2918.33 7.303 1000 2911.87 7.287 952 2905.15 7.270 25 2817.26 7.050 318 2815.67 7.046 313 2809.45 7.030 388 2808.84 7.029 347 2807.74 7.026 400 2801.03 7.009 244 2799.44 7.005 236
13C NMR
100.53 MHz | |
0.040 g : 0.5 ml CDCl3 |
MASS
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ZY 19489, MMV 253
C24 H32 FN9, 465.5
CAS 1821293-40-6
MMV253, GTPL10024, MMV674253
N-(4-cyclopropyl-5-fluoro-6-methylpyridin-2-yl)-5-((3R)-2-((1,5-dimethyl-1H-pyrazol-3-yl)amino)-3,4-dimethylpiperazin-1-yl)pyrimidin-2-amine
2-N-(4-cyclopropyl-5-fluoro-6-methylpyridin-2-yl)-5-[(3R)-3,4-dimethylpiperazin-1-yl]-4-N-(1,5-dimethylpyrazol-3-yl)pyrimidine-2,4-diamine
Nature Communications (2015), 6, 6715.
https://www.nature.com/articles/ncomms7715
Hameed P., S., Solapure, S., Patil, V. et al. Triaminopyrimidine is a fast-killing and long-acting antimalarial clinical candidate. Nat Commun 6, 6715 (2015). https://doi.org/10.1038/ncomms7715
Synthesis of (R)-N2-(4-cyclopropyl-5-fluoro-6-methylpyridin-2-yl)-N4-(1, 5-dimethyl-1H-pyrazol-3-yl)-5-(3, 4-dimethylpiperazin-1-yl)pyrimidine-2,4-diamine (12). (R)-N2-(4-cyclopropyl-5-fluoro-6-methylpyridin-2-yl)-N4-(1,5-dimethyl-1H-pyrazol-3-yl)-5-(3-methylpiperazin-1-yl)pyrimidine-2,4-diamine hydrochloride (compound 9, 190 mg, 0.42 mmol) was taken in dichloromethane (2 ml) to give a yellow suspension. To this Hunig’s Base (0.184 ml, 1.05 mmol) was added and the suspension turned clear. After 10 min of stirring, reaction mixture turned into a white suspension and then it was concentrated to dryness. Resultant residue was dissolved in ethanol (absolute, 99.5%) (3 ml), and formaldehyde (0.042 ml, 0.63 mmol) was added and stirred for 10 min. To this clear solution, sodium cyanoborohydride (26.4 mg, 0.42 mmol) was added in one portion to get a white suspension. The reaction mixture was concentrated and the crude product was purified through reverse-phase chromatography to get the pure off-white solid of (R)-N2-(4-cyclopropyl-5-fluoro-6-methylpyridin-2-yl)-N4-(1, 5-dimethyl-1H-pyrazol-3-yl)-5-(3,4-dimethylpiperazin-1-yl)pyrimidine-2,4-diamine (80 mg, 40.8%). Yield: 40.8%, purity: >95% by HPLC (ultraviolet at 220 and 254 nm). 1H NMR (300 MHz, DMSO-d6) δ 9.26 (s,1H), 8.03 (s, 1H) 8.00 (s, 1H) 7.67 (d, J=5.1 Hz, 1H) 6.83 (s, 1H) 3.33 (s, 3H) 2.96–2.73 (m, 4H) 2.75–2.50 (m, 1H) 2.38–2.30 (m, 4H) 2.23 (s, 7H) 2.10–1.96 (m, 1H),1.08–1.02 (m, 2H) 1.00 (d, J=6.2 Hz, 3H) 0.78–0.67 (m, 2H). 13C-NMR (126 MHz, DMO-d6) δ 155.30, 154.67, 152.10, 150.93, 148.98, 146.81. 145.29, 141.95, 140.31, 138.81, 124.91, 106.20, 97.07, 58.78, 51.87, 42.16, 35.28, 17.23. 10.99 and 8.77, HRMS (ESI): m/z calculated for C24H32FN9+H [M+H]: 466.2765. Found: 466. 2838. Traces of LC-MS, HRMS, 1H NMR and 13C-NMR of compound 12 are shown in Supplementary Figs 1–3.