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CAS No. : | 36936-23-9 | MDL No. : | MFCD09453335 |
Formula : | C6H7ClN2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | SHIKRPPKGCWKJO-UHFFFAOYSA-N |
M.W : | 142.59 | Pubchem ID : | 12251007 |
Synonyms : |
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Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H319 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
5.28 g (67%) | With aq. NaOH; nitric acid; | 2-Amino-5-chloro-6-methyl-3-nitropyridine (46) To stirred conc H2 SO4 (70 mL) at 0 C. was added 45 (6.0 g, 41.8 mmol) in portions. To the resulting dark brown solution was added dropwise 70% HNO3 (3.5 mL, 54 mmol) at 0 C. After the addition, the reaction mixture was stirred at 50 C. under N2 for 2.5 h, cooled to room temperature and poured into crushed ice (about 700 g). The mixture was basified to pH 9 by the addition of 40% aq. NaOH dropwise with stirring and cooling (ice-water bath). The precipitate was filtered, washed with water (4*100 mL) and MeOH (3*25 mL), and dried to give 5.28 g (67%) of 46 as a yellow powder, mp 214-5 C. (lit. 214-6 C., Cress et al., J. Org. Chem. 93-6 (1976)). 1 H NMR (DMSO-d6) delta2.445 (s, 3H), 8.011 (bs, 2H), 8.340 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-chloro-succinimide; In hexane; N,N-dimethyl-formamide; | 2-Amino-5-chloro-6-methylpyridine (45) To a stirred solution of 2-amino-6-methylpyridine (10.80 g, 100.0 mmol) in dry DMF (50 mL) was added dropwise a solution of NCS (13.35 g, 100.0 mmol) in dry DMF (60 mL) at 0 C. over 20 min. The resulting brown yellow solution was stirred at 0 C. for 1 h, and at room temperature for 3 h, then poured into ice-water (about 300 mL). The resulting mixture was extracted with EtOAc (4*100 mL). The extracts were combined, washed with brine (6*50 mL), dried (MgSO4), and rota-evaporated. To the residual viscous black oil was added hexane (200 mL) and it was heated to boiling with stirring. The hot hexane solution was decanted carefully, concentrated to about 60 ml, then allowed to stand at room temperature overnight. The resulting crystals were filtered and dried at room temperature in vacuo, giving 6.06 g (42%) of 45 as orange-colored long needles, mp 74-5 C. (lit. 73-4 C., Cress et al., J. Org. Chem. 93-6 (1976)). 1 H NMR (CDCl3) delta2.439 (s, 3H), 4.376 (bs, 2H), 6.302 (d, 1H, J=8.5), 7.340 (d, 1H, J=8.5). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With m-chloroperoxybenzoic acid; In hydrogenchloride; dichloromethane; | Step E Preparation of 5-chloro-6-methyl-2-pyridinamine 1-oxide, hydrochloride To a solution of 110 g (666 mmol) of <strong>[36936-23-9]5-chloro-6-methyl-pyridineamine</strong> (Kress, T. J.; Moore, L. L.; Costantino, S. M. J. Org. Chem. (1976) 41(1), pp 93-96) in 1 L of dichloromethane was added 164 g (666 mmol) of m-chloroperoxybenzoic acid. The mixture was stirred at room temperature overnight and 20 g more of m-chloroperoxybenzoic acid was added. The mixture was stirred 1 h and 50 mL of saturated aqueous NaHSO3 were added. The solvent was removed and the residue was taken up in 1L of 1N HCl. The insoluble solids were filtered and washed with 3N HCl. Solvent was removed from the aqueous filtrate to give a solid which was recrystallized from ethanol affording 56.9 g of 5-chloro-6-methyl-2-pyridinamine 1-oxide, hydrochloride as a white solid, mp>250 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20% | In acetonitrile; at 130℃; for 36.0h; | Step 1 Methyl 6-chloro-4-(5-chloro-6-methylpyridin-2-ylamino)pyridazine-3-carboxylate A pressure tube was charged with methyl 4,6-dichloropyridazine-3-carboxylate (2 g, 9.66 mmol) and <strong>[36936-23-9]5-chloro-6-methylpyridin-2-amine</strong> (2.76 g, 19.3 mmol). To the mixture was added acetonitrile (12 mL) and the reaction mixture heated with stirring at 130 C. for 1.5 days. After cooling to room temperature, the acetonitrile was removed in vacuo. The residue obtained was purified by chromatography (silica, 80 g, 50 mum from Analogix, 0% to 5% acetone in dichloromethane over 20 min., holding at 5% for 5 min, then increasing the gradient from 5% to 10% over the next 20 min) to give methyl 6-chloro-4-(5-chloro-6-methylpyridin-2-ylamino)pyridazine-3-carboxylate (618 mg, 20%) as an orange solid. 1H NMR (400 MHz, CHLOROFORM-d) delta ppm 10.70 (br. s., 1H), 9.18 (s, 1H), 7.63 (d, J=8.34 Hz, 1H), 6.78 (d, J=8.34 Hz, 1H), 4.12 (s, 3H), 2.66 (s, 3H), 1.58 (br. s., 1H); LC-MS 313 [M+H]+. |