2-Chloro-5-nitropyrimidine

Light yellow solid

A mixture of 2-hydroxy-5-nitropyrimidine (1.Og, 7.1mmol) and N, N-dimethylaniline (0.9mL, 7.1mmol) in POCl (270 mg, 1.69 mmol) was dissolved in THF (60 ml) and 4- (piperazin-l-yl)benzonitrile (317 mg, 1.69 mmol) was added. The reaction mixture turned immediately yellow. The reaction mixture was concentrated under vacuum. The crude was diluted in H20 and extracted with EtOAc and DCM. The combined organic layers were dried with MgS04 and concentrated under vacuum. The crude product was purified with flash chromatography (silica gel, 120 g, 0% to 5% MeOH in DCM) to yield 4-(4-(5-nitropyrim- idin-2-yl)piperazin-l-yl)benzonitrile (150 mg, 27% yield) as an orange solid. LC-MS: m/z = 311.1 [M+H]+ (270 mg, 1.69 mmol) was dissolved in THF (60 ml) and 6- (piperazin-l-yl)nicotinonitrile (319 mg, 1.69 mmol) was added. The reaction mixture turned immediately yellow. The reaction mixture was concentrated under vacuum. The crude was diluted in H20 and extracted with EtOAc and DCM. The combined organic layers were dried with MgS04 and concentrated under vacuum. The crude product was purified with flash chromatography (silica gel, 120 g, 0% to 5% MeOH in DCM) to yield 6-(4-(5-nitropyrim- idin-2-yl)piperazin-l-yl)nicotinonitrile (246 mg, 44% yield) as an orange solid. LC-MS: m/z = 312.1 [M+H]+. (2.0 g, 12 mmol) was dissolved in THF (60 ml). l-(Pyridin- 2-yl)piperazine (2.2 g, 2.1 ml, 14 mmol) was added. After completion of the reaction as mon itored by TLC, the mixture was concentrated under vacuum. The crude was diluted with H20 and extracted with EtOAc and additional portions of DCM. The combined organic layers were dried with MgS04 and concentrated under vacuum. The product was purified by flash chromatography (silica gel, 120 g, 0% to 5% MeOH in DCM) to yield 5-nitro-2-(4-(pyridin- 2-yl)piperazin-l-yl)pyrimidine (1.07 g, 30%) as an orange solid. LC-MS: m/z = 287.2 [M+H]+.NaH (60percent) oil dispersion, 8 g, 333 mmol) was added to a solution of l-methyl-4- hydroxypiperidine (18 g, 156 mmol) in dry DMF (200 mL) at 6 °C. The solution was stirred at room temperature for 30 min and a solution of (3S)-1o-(3-aminopyrrolidin- 1-yl)-9-fluoro-3-methyl-7-oxo-2, 3-dihydro-7H- [1, 4]oxazino[2, 3, 4-ij]quinoline-6-carboxylic acid (40 mg, 0.115 mmol, 1 eq) was dissolved in dimethyl sulfoxide (2 mL) with 2-Chloro-5-nitropyflmidine (36.74 mg, 0.230 mmol, 2 eq) in a s mL capacity microwave vessel fitted with a magnetic stirrerbar and microwaved at 160°C for 1.5 hours. The DMSO was evaporated the compound was crystalized using hot ethanol to afford compound A1.27. 1H NMR (400 MHz, DMSO-d6) 6 15.38 (br. s., 1H), 9.15 (d, J = 3.30 Hz, 1H), 9.08 (d, J= 3.30 Hz, 1H), 8.90 (s, 1H), 7.56 (d, J = 14.12 Hz, 1H), 4.90-4.85 (m, 1H), 4.60 - 4.56 (m, 1H), 4.53 (d, J = 11.74 Hz, 1H), 4.28 (d, J = 11.19 Hz, 1H), 4.05 ' 3.90 (m, 2H), 3.75 - 3.83-3.68 (m, 2H), 2.22 (tcl, J = 6.53, 12.79 Hz, 1H), 2.05 (dcl, J = 6.51, 12.56 Hz, 1H), 1.45 (ci, J = 6.79 Hz, 3H); Formula C21H19FN606 LC-MC Retention time 3.362 mm, Found 471.1 [M+H]At room temperature, Diethylphenyl malonate (21.64 mL) was suspended in DMF (100 mL) solution and ice cooled, and 60percent NaH (4.02 g) was added and was stirred for 30 minutes, after which

Molecular Weight:159.53
XLogP3:1
Hydrogen Bond Acceptor Count:4
Exact Mass:158.9835540
Monoisotopic Mass:158.9835540
Topological Polar Surface Area:71.6
Heavy Atom Count:10
Complexity:129
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes