HCID 59168801, compound → HCID 25065409, compound

HRID 421457Notes

Reaction equation

[CH3:1][S:2]([NH:5][CH2:6][C:7]1[C:8]([S:15]([NH2:18])(=[O:17])=[O:16])=[C:9]([N+:12]([O-])=O)[S:10][CH:11]=1)(=[O:4])=[O:3]>[Pd].O1CCCC1>[NH2:12][C:9]1[S:10][CH:11]=[C:7]([CH2:6][NH:5][S:2]([CH3:1])(=[O:4])=[O:3])[C:8]=1[S:15]([NH2:18])(=[O:16])=[O:17]

Participants

Conditions

Temperature: 25 °C

Procedure

Palladium on carbon (12 g, 10%, activated, Aldrich) was added to a solution of 4-(methanesulfonylamino-methyl)-2-nitro-thiophene-3-sulfonic acid amide (prepared as described in Example 1g; 15 g, 47.6 mmol) dissolved in tetrahydrofuran (150 mL). The flask was degassed and backfilled with hydrogen gas. The mixture stirred under an atmosphere of hydrogen gas (balloon) for 20 h at 25° C. and then was filtered through Celite. The filtrate was concentrated in vacuo to afford 2-amino-4-(methanesulfonylamino-methyl)-thiophene-3-sulfonic acid amide as a thick golden oil. The oil was dissolved in N,N-dimethylformamide (150 mL) and 3,3-diethoxy-acrylic acid ethyl ester (10.62 g, 56.4 mmol) was added. A slow stream of nitrogen gas was applied to the atmosphere above the reaction mixture and the solution stirred at 70° C. for 5 h. Triethylamine (19 g, 188 mmol) was added directly to the reaction mixture and the solution continued to stir for 1 h. Upon cooling, the solution was concentrated in vacuo to reduce the total volume to 25 mL. The mixture was diluted with ethyl acetate (150 mL) and washed with 1.0 M aqueous hydrochloric acid solution (1×50 mL) followed by saturated aqueous brine solution (1×50 mL). The aqueous phase was back extracted with ethyl acetate (1×25 mL). The organic phases were combined, passed through a plug of silica gel (Merck silica gel 60, 40-63 μm) and concentrated in vacuo to afford a thick oil. The oil was dissolved in ethyl acetate (30 mL) and was stored at 25° C. for 16 h. The resulting solid was collected by vacuum filtration (10.75 g). The filtrate was concentrated in vacuo to afford a thick oil. The residue was purified by flash column chromatography (Teledyne Isco RediSep column; 40-100% ethyl acetate in hexanes) to afford a solid (3.23 g) which was combined with the solid from above followed to afford [7-(methanesulfonylamino-methyl)-1,1-dioxo-1,4-dihydro-1λ6-thieno[2,3-e][1,2,4]thiadiazin-3-yl]-acetic acid ethyl ester (13.98 g, 36.7 mmol, 77%) as a beige powder.

Workup

customThe flask was degassed
filtrationwas filtered through Celite
concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record: ord-cf086e4ab73a46b48cc47078eec2fa46
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08097613B2

Reaction notes

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