HCID 10293956, compound → HCID 69662788, compound

Participants

Reaction Conditions

Reaction Steps

To methanol heated to 60° C. (63 L) was added 2-(aminomethyl)-3-chloro-4-(4-methoxyphenyl)-7-oxido-5,8-dihydro-6H-thiopyrano[4′,3′:4,5]thieno[2,3-b]pyridine (6.5 kg) and the mixture was stirred for 5 minutes, followed by addition of (R)-(−)-hydrogenphosphate-1,1′-bihaphthyl-2,2′-diyl (3.455 kg). The mixture was stirred at 60° C. for 10 minutes, slowly cooled to 25° C. After stirring for 1 hours, crystals were filtered off and washed with methanol (13L). Methanol-ethanol (1:3, 63 L) was heated to 75° C. and the resultant crystals were added thereto. The mixture was slowly cooled to 25° C. and stirred for 1 hours. Crystals deposited were filtered off and washed with methanol-ethanol (1:1, 13 L). The crystals were dissolved in tetrahydrofuran-water (3:1, 121. 4 L) and active carbon (242 g) was added thereto. The mixture was stirred at room temperature for 15 minutes and the active carbon was filtered off. The tetrahydrofuran layer was distilled off under reduced pressure and the resultant aqueous layer was stirred at 25° C. to deposit crystals. The crystals were filtered off to obtain a diastereomer salt of (S)-2-(aminomethyl)-3-chloro-4-(4-methoxyphenyl)-7-oxido-5,8-dihydro-6H-thiopyrano[4′,3′:4,5]thieno[2,3-b]pyridine with (R)-(−)-hydrogenphosphate-1,1′-binaphthyl-2,2′-diyl (4.618 kg, 37.7%). 1H-NMR (DMSO-d6) δ: 1.98-2.04 (1H, m), 2.35-2.43 (1H, m), 2.71-2.81 (1H, m), 3.01-3.06 (1H, m), 3.83 (3H, s), 3.18 (1H, d, J=17.1 Hz), 4.26 (1H, d, J=17.1 Hz), 4.35 (2H, s), 0.07-7.43 (12H, m), 7.96-8.10 (4H, m), 8.64 (3H, bs).

Provenance & Evidence