Related Products of 1258298-01-9, A common heterocyclic compound, 1258298-01-9, name is 2,6-Dichloro-4-iodobenzoic acid, molecular formula is C7H3Cl2IO2, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
4-Amino-2,6-dichloro-phenol (50 g) was treated with B0C2O (69g ) in 1 ,4-dioxane (0.8 L) at reflux for 18h before the volatiles were removed in vacuo affording (3,5-dichloro-4-hydroxy-phenyl)-carbamic acid fert-butyl ester (70 g), which was used for next step without further purification. This procedure was repeated to afford more of this material. 86 g of the compound and 2,6-dimethylpyridine (49 g) were dissolved in DCM (0.9 L). Tf20 (104 g) was added drop-wise at -78 C. The mixture was allowed to warm to room temperature whereafter it was stirred for 2h. The crude mixture was partitioned between water and DCM. The organic layer was dried over Na2S04, filtered, and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluent: petane:EtOAc 30: 1) to afford trifluoro-methanesulfonic acid 4-fert-butoxycarbonylamino-2,6- dichloro-phenyl ester (73 g). This material was mixed with Pd(DPPF)Ci2 (4 g), triethylamine (102 mL) in a mixture of methanol (580 mL) and DMF (384 mL). The mixture was refluxed under an atmosphere of carbon monoxide overnight before it was cooled, concentrated in vacuo. The residue was partitioned between water and EtOAc. The organic layer was washed with brine, dried over Na2S04, filtered, and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluent: pentane:EtOAc 80: 1) to afford A-tert- butoxycarbonylamino-2,6-dichloro-benzoic acid methyl ester (12 g). 7 g of this material was dissolved in 37% aq HC1 (70 mL), and a solution of sodium nitrite (3.75 g) in water (100 mL) was added drop-wise at 0 C. The mixture was stirred for 30 min at 0 C before it was filtered and the filtrate was added to a pre-cooled solution of potassium iodide (24 g) at 0 C. The mixture was warmed to room temperature and stirred overnight. The mixture was extracted with EtOAc. The organic layer was washed with sat. aq NaHSC>3 before it was dried over Na2S04, filtered, and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluent: pentane:EtOAc 50: 1) to afford 2,6-dichloro-4-iodo- benzoic acid methyl ester (7.9 g). This material was dissolved in a mixture of pyridine (40 mL) and water (7 mL) and treated with lithium iodide (3.2 g) at 130 C for 30h before the volatiles were removed in vacuo. The residue was partitioned between 2M aq HC1 and EtOAc. The organic layer was concentrated in vacuo to afford 2,6-dichloro-4-iodo-benzoic acid (3 g). 0.5 g of this material was stirred in thionyl chloride (8 mL) at 60 C for 3h before excess thionyl chloride was removed in vacuo. The residue was washed with ether and dried to afford 2,6-dichloro-4-iodo-benzoyl chloride (0.53g) that was used directly in the next step where it was dissolved in a mixture of DMF (20 mL) and DIPEA (0.57 mL). To this solution was added lid (277 mg). The mixture was stirred at room temperature for lh. The volatiles were removed in vacuo, and residue was purified by chromatography on silica gel (eluent: DCMMeOH 100:1 to 30:1) to afford 2,6-dichloro-4-iodo-benzoic acid N’-(2-methyl- pyrido[2,3-b]pyrazin-3-yl)-hydrazide (250 mg). This procedure was repeated to afford more material. 380 mg of the compound was dissolved in 1 ,4-dioxane (5 mL). Phosphoryl chloride (4 mL) was added, and the mixture was stirred at 90 C for 1.5h. The volatiles were removed in vacuo. The residue was partitioned between DCM and water. The organic layer was washed with sat. aq. NaHCOs, dried over NaSO i, filtered, and concentrated in vacuo. The residue was purified by preparative TLC (eluent: pentane:EtOAc 2:1) to afford example Id6 (45.5 mg). LC/MS (method WXE-AB10): RT(PDA) = 2.39 min; PDA/ELS purities 97.1% / 98.3%; mass observed 456.0.
The synthetic route of 1258298-01-9 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; H. LUNDBECK A/S; J?RGENSEN, Morten; BRUUN, Anne Techau; RASMUSSEN, Lars Kyhn; WO2013/34761; (2013); A1;,
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com