Pyridine → HCID 57504946, compound

HRID 2060805Notes

Reaction equation

[OH:1][C@H:2]1[CH2:19][C@:5]2([C:20]3[CH:21]=[C:22]([C:26]4[CH:31]=[CH:30][CH:29]=[C:28]([O:32][CH3:33])[CH:27]=4)[CH:23]=[CH:24][CH:25]=3)[N:6]=[C:7]([NH:10]C(=O)C3C=CC=CC=3)[S:8][CH2:9][C@@H:4]2[CH2:3]1.CO[NH3+].[Cl-:37].N1C=CC=CC=1>C(O)C>[ClH:37].[NH2:10][C:7]1[S:8][CH2:9][C@@H:4]2[CH2:3][C@@H:2]([OH:1])[CH2:19][C@:5]2([C:20]2[CH:21]=[C:22]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([O:32][CH3:33])[CH:27]=3)[CH:23]=[CH:24][CH:25]=2)[N:6]=1

Participants

Conditions

Temperature: 50 °C

Procedure

A mixture of N-((4aR,6R,7aS)-6-hydroxy-7a-(3′-methoxybiphenyl-3-yl)-4,4a,5,6,7,7a-hexahydrocyclopenta[d][1,3]thiazin-2-yl)benzamide (0.061 g, 0.133 mmol), o-methylhydroxylamine hydrochloride (0.111 g, 1.3 mmol) and pyridine (0.105 g, 1.30 mmol) in ethanol (5 mL) is heated to 50° C. for 15 h. The mixture is concentrated under reduced pressure. The crude product is purified by silica gel chromatography eluting with 0.5% to 10% NH3 (7 N solution in methanol) in dichloromethane over 30 minutes to afford the title compound as a freebase (0.041 g, 87%). ES/MS m/e: 355 (M+1). A 1 N solution of HCl in Et2O (0.139 mL, 0.139 mmol) is added to a solution of (4aR,6R,7aS)-2-amino-7a-(3′-methoxybiphenyl-3-yl)-4,4a,5,6,7,7a-hexahydrocyclopenta[d][1,3]thiazin-6-ol (0.041 g, 0.116 mmol) in minimal dichloromethane and methanol. The solvent is removed under reduced pressure to give the title compound (0.045 g, 86%). ES/MS m/e: 355 (M+1).

Workup

concentrationThe mixture is concentrated under reduced pressure
customThe crude product is purified by silica gel chromatography
washeluting with 0.5% to 10% NH3 (7 N solution in methanol) in dichloromethane over 30 minutes

Sources & evidence

ORD record: ord-9b8428d8d7714f1e9559ac2d1fc46a36
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08278441B2

Reaction notes

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