Ethyl orthoformate → HCID 86709285, compound

HRID 517302Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([N:24]2[CH2:29][CH2:28][CH:27]([C:30]([NH2:33])=[N:31][OH:32])[CH2:26][CH2:25]2)[CH:5]=[CH:6][C:7]=1[CH2:8][N:9]1[C@@H:14]([CH3:15])[CH2:13][CH2:12][CH:11]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[S:10]1(=[O:23])=[O:22].[CH:34](OCC)(OCC)OCC>FC(F)(F)C(O)=O>[F:1][C:2]1[CH:3]=[C:4]([N:24]2[CH2:29][CH2:28][CH:27]([C:30]3[N:33]=[CH:34][O:32][N:31]=3)[CH2:26][CH2:25]2)[CH:5]=[CH:6][C:7]=1[CH2:8][N:9]1[C@@H:14]([CH3:15])[CH2:13][CH2:12][CH:11]([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[S:10]1(=[O:22])=[O:23]

Participants

Conditions

Temperature: 100 °C

Procedure

A solution of 1-[3-fluoro-4-[[(3S)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]phenyl]-N′-hydroxy-piperidine-4-carboxamidine Stereoisomer A (150 mg, 0.32 mmol) in triethyl orthoformate (2 mL) was heated to 100° C. for 1 hour. 2 drops of trifluoroacetic acid were then added and the reaction was stirred at 100° C. for 1 hour. The solution was then concentrated and purified by preparative HPLC to give (3S)-2-[[2-fluoro-4-[4-(1,2,4-oxadiazol-3-yl)-1-piperidyl]phenyl]methyl]-3-methyl-6-phenyl-thiazinane 1,1-dioxide Stereoisomer A (31.8 mg, 21% yield). 1H NMR (400 MHz, DMSO) δ 9.53-9.49 (s, 1H), 7.49-7.43 (m, 2H), 7.43-7.35 (m, 3H), 7.35-7.29 (m, 1H), 6.85-6.79 (m, 1H), 6.77-6.69 (m, 1H), 4.50-4.36 (m, 2H), 4.32-4.23 (m, 1H), 4.15-4.02 (m, 1H), 3.81-3.69 (m, 2H), 3.13-3.01 (m, 1H), 2.97-2.83 (m, 2H), 2.46-2.37 (m, 1H), 2.14-1.97 (m, 3H), 1.89-1.70 (m, 3H), 1.70-1.59 (m, 1H), 1.13-1.05 (d, J=6.8 Hz, 3H); LCMS [M+1]+=485.2.

Workup

concentrationThe solution was then concentrated
custompurified by preparative HPLC

Sources & evidence

ORD record: ord-5e5d84eb43864afeba2eab4c620c0f7c
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09115101B2

Reaction notes

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