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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 1072-72-6 |
Formula : | C5H8OS |
M.W : | 116.18 |
SMILES Code : | O=C1CCSCC1 |
MDL No. : | MFCD00006660 |
InChI Key : | OVRJVKCZJCNSOW-UHFFFAOYSA-N |
Pubchem ID : | 66173 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | To a mixture of tetrahydrothiopyran-4-one (5.14 g) and conc. hydrochloric acid (20 mL) was added sodium azide (4.31 g) under ice-cooling. The reaction mixture was stirred at room temperature for 4 hrs., and sodium carbonate was added. The mixture was diluted with iced water and extracted with chloroform. The organic layer was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated to give 1,4-thiazepan-5-one as crystals (3.62 g, yield 62%). Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 120-121C. | |
(Ref: J. Org. Chem. 1960, 25, 1953-1956.) To a stirred solution of tetrahydrothiopyran-4-one 1 (10 g, 86 mmol) in cone. HCl (43 mL) cooled to 0 0C is added sodium azide (8.4 g, 129 mmol) portionwise over 30-60 min, (note: gas evolution). When the addition is complete the reaction mixture is stirred at RT for 4 h.The mixture is cooled to 0 0C and solid Na2CO3 is added portionwise (note: gas evolution), plus water to dissolve the salts, until the solution is alkaline ~pH 9. The alkaline solution is diluted with DCM (200 mL), the phases are seperated and the aqueous layer is extracted with DCM (3 x 100 mL). The combined organic layers are EPO <DP n="24"/>dried over MgSOphi filtered and concentrated to a low volume (-20 mL), petroleum ether is added and the solid is collected by filtration and dried to afford the title compound as a white solid: 1H NMR (400 MHz, DMSO) delta 7.52 (s, IH), 3.39 (m, 2H), 2.63 (m, 2H), 2.58 (m, 4H); MS-APCI (m/z+-) 131.9 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With toluene-4-sulfonic acid; In ethyl acetate; toluene; | (a) To a solution of 15 g of 4H-tetrahydrothiopyran-4-one in 500 mL of toluene, 25 g of <strong>[6296-99-7]diethyl aminomethylenemalonate</strong> and 0.8 of p-toluenesulfonic acid are added. The resultant mixture is refluxed for 48 hours with a water separator under nitrogen atmosphere, then evaporated to dryness. The dried residue is purified by flash chromatography on a silica gel column, using toluene and 5percent ethyl acetate in toluene as eluents to obtain the desired product, diethyl N-(2H-5,6-dihydrothiopyran-4-yl)aminomethylenemalonate. | |
With toluene-4-sulfonic acid; In ethyl acetate; toluene; | (a) To a solution of 15 g of 4H-tetrahydrothiopyran-4-one in 500 mL of toluene, 25 g of <strong>[6296-99-7]diethyl aminomethylenemalonate</strong> and 0.8 g of p-toluenesulfonic acid are added. The resultant mixture is refluxed for 48 hours with a water separator under nitrogen atmosphere, then evaporated to dryness. The dried residue is purified by flash chromatography on a silica gel column, using toluene and 5percent ethyl acetate in toluene as eluents to obtain the desired product, diethyl N-(2H-5,6-dihydrothiopyran-4-yl)-aminomethylenemalonate. | |
With toluene-4-sulfonic acid; In ethyl acetate; toluene; | (a) To a solution of 15 g of 4H-tetrahydrothiopyran-4-one in 500 mL of toluene, 25 g of <strong>[6296-99-7]diethyl aminomethylenemalonate</strong> and 0.8 g of p-toluenesulfonic acid are added. The resultant mixture is refluxed for 48 hours with a water separator under nitrogen atmosphere, then evaporated to dryness. The dried residue is purified by flash chromatography on a silica gel column, using toluene and 5percent ethyl acetate in toluene as eluents to obtain the desired product, diethyl N-(2H-5,6-dihydrothiopyran-4-yl)aminomethylenemalonate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
4.30 g (81%) | With sodium carbonate; In hydrogenchloride; water; | Preparation 34 1,4-Thiazepane To a stirred solution of tetrahydrothiopyran-4-one (4.74 g) in conc. HCl (20.7 mL) cooled to 0 C. is added portion-wise sodium azide (3.98 g, 61.2 mmol). After addition is complete, the reaction is stirred at room temperature for 4 h. Solid sodium carbonate is then added portion-wise until the solution was slightly alkaline (pH=9). Water is added during addition of sodium carbonate to dissolve the salt. The alkaline solution is diluted with CHCl3 (125 mL), and the phases are separated. The aqueous layer is extracted with CHCl3 (2*75 mL). The combined organic layers are dried (Na2SO4), filtered, and concentrated. The crude product is recrystallized from CH2Cl2/hexanes to afford 4.30 g (81%) of 1,4-thiazepan-5-one as a white solid. Physical characteristics are as follows: Mp 114-116 C.; 1H NMR (300 MHz, CDCl3) delta6.41, 3.66, 2.96, 2.76. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | A solution of 4-bromo-N-Boc aniline (6.0 g, 22.1 mmol) in THF (100 ml) at -78 0C under nitrogen was added n-butyllithium (1.6 M in hexane, 34.4 ml, 55 mmol) dropwise over 20 min. The resulting yellow solution was stirred at -78 0C for 30 min and was then treated with a solution of tetrahydrothiopyran-4-one (2.82 g, 24.3 mmol) in THF (25 mi_). The reaction mixture was stirred for 4 hrs, during which the reaction temperature was allowed to rise to 0 0C. The eraction was quenched with saturated aqueous ammonium chloride (25 ml). The mixture was then diluted with water (25 ml) and Et2O (25 ml). The layers were separated, and the organic phase was washed with brine (10 ml), dried over Na2SO4, and concentrated in vacuo. The residue was flushed through a plug of silica gel with EtOAc: Heptane (1:1) to afford tert-butyl 4-(4-hydroxy-tetrahydro-2H-thiopyran-4-yl)phenylcarbamate (6.2 gram, 92%) as a white solid. 1H NMR (400 MHz1 d-CDCI3) delta 7.30 - 7.41 (m, 4 H) 6.44 (br. s., 1 H) 3.13 - 3.24 (m, 2 H) 2.41 - 2.50 (m, 2 H) 2.09 - 2.19 (m, 2 H) 1.95 - 2.03 (m, 2 H) 1.50 (s, 9 H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | The title compound can also be prepared according to the following procedure: TMSOTf (1.4 ml_, 7.7 mmol) was added dropwise to a solution of tetrahydro-4H-thiopyran- 4-one (0.88 g, 7.6 mmol) in DCM (80 ml.) in the presence of molecular sieves at 0 0C (bath temp). A solution of ethyl 5-bromo-1 /-/-indole-7-carboxylate (2 g, 7.4 mmol). in DCM (20 ml.) was added and the reaction was stirred for 15 min. Triethylsilane (2 ml_, 12.5 mmol) was added and the reaction was allowed to warm to room temperature overnight. Saturated aqueous Na2CO3 was added, the layers separated and the aqueous layer extracted with DCM. The combined organic layers were dried (Na2SO4) and concentrated under reduced pressure. The residue was washed with MeOH and dried in a vacuum oven, giving 2.07 g (76%) of the title compound. |