Methanesulfonic Acid → HCID 178461645, compound

Participants

Reaction Conditions

Reaction Steps

As shown in step v of Scheme 1, (S)-2-(quinolin-6-yl)propanoic acid (50 g, 248.5 mmol) and 1,3-diaminothiourea (29.02 g, 273.4 mmol) were suspended in a mixture of tetramethylene sulfone (sulfolane, 38 mL) and water (57 mL). Methane sulfonic acid (35.5 ml, 546.7 mmol) was added to the mixture, whereupon all solids dissolved. The reaction temperature was slowly increased to 90° C. and the reaction was heated at 90° C. for 40 hours, at which time a 68% conversion of starting material to product was observed by HPLC analysis. The reaction mixture was cooled in an ice bath and water (75 mL) was added, followed by the careful addition of saturated sodium bicarbonate (500 mL) until a pH 8 was achieved. The resulting fine purple precipitate was collected by vacuum filtration, washed with water, saturated sodium bicarbonate, water, and methyl t-butyl ether, respectively. The product was dried in a vacuum oven at 55° C. for 2 days to afford 6-((S)-1-(5-mercapto-4-amino-4H-1,2,4-triazol-3-yl)ethyl)quinoline (compound 1005, 43 g): ESMS (M+1), 272.09; 1H NMR (300.0 MHz, DMSO-d6) δ 13.65 (1H, br s), 8.86 (1H, dd, J=1.8, 8.4 Hz), 8.34 (1H, d, J=7.5 Hz), 7.98 (1H, d, J=8.7 Hz), 7.84 (1H, dd, J=1.7, 13.7 Hz), 7.82 (1H, d, J=1.5 Hz), 7.70 (1H, dd, J=1.8, 8.7 Hz), 7.50 (1H, dd, J=1.8, 8.7 Hz), 5.44 (2H, s), 4.57 (1H, q, J=7.2 Hz), 1.65 (3H, d, J=7.2 Hz). The product was 92% pure by 1H NMR analysis, with the major impurities being compound 1004 and sulfolane. Chiral HPLC analysis showed 92% ee (ChiralPak® AD-H, 70% i-propanol/hexanes; retention time: 4.98 min for S-enantiomer, 12.33 min for R-enantiomer). The product was used as is in the next step without further purification.

Provenance & Evidence