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[ CAS No. 1002-18-2 ] {[proInfo.proName]}

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Chemical Structure| 1002-18-2
Chemical Structure| 1002-18-2
Structure of 1002-18-2 * Storage: {[proInfo.prStorage]}
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Product Details of [ 1002-18-2 ]

CAS No. :1002-18-2 MDL No. :MFCD19439722
Formula : C6H8Cl2O2S2 Boiling Point : -
Linear Structure Formula :- InChI Key :VURCJRMYKFUQSW-UHFFFAOYSA-N
M.W : 247.16 Pubchem ID :11195974
Synonyms :

Safety of [ 1002-18-2 ]

Signal Word:Danger Class:8
Precautionary Statements:P264-P270-P271-P280-P303+P361+P353-P304+P340-P305+P351+P338-P310-P330-P331-P363-P403+P233-P501 UN#:3265
Hazard Statements:H302-H314 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 1002-18-2 ]

* 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.

  • Downstream synthetic route of [ 1002-18-2 ]

[ 1002-18-2 ] Synthesis Path-Downstream   1~16

  • 1
  • [ 1119-62-6 ]
  • [ 1002-18-2 ]
YieldReaction ConditionsOperation in experiment
99% With oxalyl dichloride; In dichloromethane; at 20℃; for 12h; 3-(2-carboxy-ethyldisulfanyl)-propionic acid (420 mg, 0.2 mmol) and oxalyl chloride (1 mL) were dissolved and stirred in dry DCM (10 mL) at room temperature for 12 h, the solvent removed by rotary evaporation, to give 489 mg (99.0%) of solid
77% With thionyl chloride; In toluene; Preparation of 3,3'dithio dipropionyl dichloride (VII) 3,3'dithio dipropionic acid (VI) (19 grams; 0.09 moles) was suspended in anhydrous toluene (300 ml.) and thionyl chloride (19 ml; 0.26 moles) was added to the resulting mixture which was then kept at 90 C. for 20 hours. 18 grams (yield: 77%) of 3,3'dithio dipropionyl dichloride (VII) were obtained which were used as such in the subsequent step.
With pyridine; sodium hydroxide; thionyl chloride; EXAMPLE 2 Preparation of 3,3'-Dithiodipropionyl chloride To a 300 ml round bottom flask fitted with a mechanical stirrer, nitrogen inlet and an outlet to a 10% sodium hydroxide trap was charged 169 g (1.42 M) of thionyl chloride and 100 g (0.48 M) of <strong>[1119-62-6]3,3'-dithiodipropionic acid</strong>. The slurry was stirred and 0.5 ml of pyridine was charged. The mixture was stirred overnight. Excess thionyl chloride was then removed under house vacuum at room temperature until bubbling ceased and then for an additional 1.5 h at 40-50 C. The resulting orange liquid of 3,3'-dithiodipropionyl chloride was used in Example 3 without further purification.
With pyridine; thionyl chloride; at 22℃; for 16h; Thionyl chloride (69.2 mL, 951 mmol) was added to a mixture of dithiopropionic acid (50.0 g, 238 mmol) and pyridine (0.1 mL) at 22C followed by stirring for 16 hours. The reaction mixture was vented into a scrubbing solution of KOH in water to trap the resulting HCl produced in this reaction. The mixture started out heterogeneous and became a clear amber solution after stirring overnight. The mixture was concentrated in vacuo to give 62 g of Compound IA as a yellow oil. This was stored under argon at 00C.
With thionyl chloride; In chloroform; for 1h;external cooling; heated; A mixture of 21.4 g 2,2-dithiodipropionic acid in 100 ml chloroform and 24.0 g thionyl chloride are added in small amounts, maintaining the temperature by external cooling. After completion of the addition the mixture is heated to remove the formed gases and the reaction was finished. The solvent is removed by distillation under low pressure and the acid chloride used as starting compound in the 2nd reaction step.
With thionyl chloride; at 80 - 100℃; for 3 - 6h; Example 140; 2-tert-Butyl-5-chloro-isothiazolin-3-one-1,1-dioxide [(2.3 g, 10 mmol)-prepared following general procedure AB) was coupled with 3-boc-amino-phenylboronic acid (3.0 g, 12 mmol) according to general procedure AC to give [3-(2-tert-butyl-1,1,3-trioxo-2,3-dihydro-1H-isothiazol-5-yl)-phenyl]-carbamic acid tert-butylester.; General Procedure AB: Preparation of N-alkyl 5-chloro-isothiazole-sulfones: Dithio-acid (1.0 eq) was dissolved in thionyl chloride (0.1-0.5 M) and the mixture was heated at 80-100 C. for 3 to 6 hours. At completion, the excess thionyl chloride was removed under pressure and compound was dried under vacuum and resulted white solid was used directly in the next step. Tert-butylamine (1.0 eq) was dissolved in dry DMF (0.1-0.5 M) and 5 eq of NaHCO3 was added. While stirring under nitrogen on ice, a solution of aryl/alky acetyl chloride (1.1 eq) in benzene was added drop wise. The mixture was then stirred for one hour and allowed to warm to room temperature. The reaction mixture was diluted with water/EtOAc and the layers separated. The aqueous layer was extracted with EtOAc and the organic layers combined and washed with water and brine. The organic solution was then dried over Na2SO4, filtered, and the filtrate was concentrated and the residue was dried and used directly in the next step. A solution of di-amide (1.0 eq) was dissolved in anhydrous dichloromethane (0.1-0.5M) and was treated with sulfuryl chloride (1.1 eq) drop-wise at 0 C. and stirred at 25 C. for 3 to 6 hours. At completion, the reaction mixture was cooled to 0 C., quenched with water and stirred for 10 to 30 min. The organic layer was separated and aqueous layer was re-extracted with dichloromethane. The combined organic layers were dried with MgSO4, filtered and concentrated to a light brown oil. The crude oil was purified by flash column chromatography (100% hexane to 40% ethyl acetate/hexane to 100% ethyl acetate) to yield off white solid. To a solution of isothiazole compound (1 eq) in 1:1 DCM/HOAc (0.1-0.5 M) was added peracetic acid (32 wt. % solution in acetic acid, 10 eq) at 0 C. and the solution was stirred at the same temperature for 2 to 6 hours. At completion, the reaction mixture was diluted with water/EtOAc. The combined organic layer washed with water, saturated NaHCO3 and brine. The organic phase was then dried over Na2SO4, filtered, and concentrated. The residue was triturated several times with hexanes to afford the desired isothiazole-sulfone derivative.
With thionyl chloride; Example 5: Synthesis of the dienic binding units L 1960 and L 1995 (Fig. 17)Tetrazine monocarboxylic acid (c.f. PCT/EP2007/005361) is reacted with thionyl chloride to obtain the respective acid chloride which is reacted with mono-boc-1,3 di- amino propane in the presence of Hiinig Base. The amide is obtained after recrystallization from acetone with a good yield. The cleavage of the boc-group is carried out with trifluoroacetic acid (TFA) in DCM. The trifluoromethanesulfonic acid (triflat) of the amine is obtained in crystalline form and can be directly used. The reaction of this compound with 3-(triethoxysilyi)-propylisocyanate in the presence of Hiinig Base provides the urea compound L 1960. After purification by column chromatography the silyl compound is obtained as a solid.The reaction of 2 equivalents of the "triflat" with 1 equivalent di-acid chloride of dithiodipropionic acid (obtained by the reaction of the acid with thionyl chloride) provides the tetrazine disulfide L 1995. The purification is made after column chromatography by recrystallization from acetone. Yield: 50-70%
With oxalyl dichloride; In N,N-dimethyl-formamide; acetonitrile;Product distribution / selectivity; Example 6: Synthesis of the diamides of dithio-dipropionic acid (Fig. 18) This synthesis is an alternative to obtain binding units with a disulfide bridge. The acid dichloride of dithio-dipropionic acid is obtained by reacting dithio-dipropionic acid with oxalylchloride in DMF/acetonitrile. This compound is reacted in-situ with mono-boc protected diamines. The thus obtained diamides are purified by recrystallization. These diamides are then reacted with TFA in dichloromethane and the respective diamines are obtained as "triflats". These are stirred with aqueous sodium carbonate solution to obtain the free amines. If the diamine is reacted with a double amount of Reppe anhydride in ethanol under conditions known in the art, the diimide is obtained in a satisfactory amount. The purification is made by recrystallization. The mass spectrum and 1H-NMR confirm the structures. By using this synthesis concept a number of dienes and dienophiles can be coupled to the disulfide compound. The reaction of the diamine with the Reppe anhydride (Fig. 16) provides the disulfide F 737 with a good yield. The reaction with the tetrazine acid chloride (Fig. 17) provides the respective tetrazine disulfide
With oxalyl dichloride; In ethyl acetate; N,N-dimethyl-formamide; for 0.333333h;Inert atmosphere; (0189) Intermediate 4: 3,3'-Dithiopropionic acid (0.459 g, 2.18 mmol) was suspended in 20 mL EtOAc, and oxalyl chloride (0.58 mL, 6.65 mmol) was added under nitrogen, followed by DMF (0.05 mL). After 20 min the reaction was evaporated to an off-white film. This was redissolved in 15 mL dry DCM, and 3-amino-4-methoxybenzanilide (1.04 g, 4.3 mmol) was added, followed by N,N-diisopropylethylamine (DIEA) (0.78 mL, 4.49 mmol) and an additional 20 mL DCM. After 80 min the dense white slurry was filtered through a medium glass frit, rinsed with 2x20 mL DCM, 2x25 mL 1 M HCl, 2×25 mL 1 M NaOH, 2x50 mL water, and evaporated to dryness to yield the symmetrical disulfide, Intermediate 4, as an off-white solid (0.937 g, 65%). ES (+) MS m/e = 659 (M+1).
With thionyl chloride; In neat (no solvent);Inert atmosphere; Reflux; Example 5 3,3'-Dithiodipropanoyl Chloride Synthesis (Larger Batch Size) In an oven dried, two-neck 250 mL round bottom flask fixed with a condenser, alkaline scrubber between the condenser and nitrogen line, and an addition funnel, 34.6 g (164.6 mmol, 1.00 eq) of <strong>[1119-62-6]3,3'-dithiodipropionic acid</strong> was added. With stirring under N2 at 23 C., 60.0 mL (827.1 mmol, 5.00 eq) of SOCl2 was added dropwise via addition funnel over a period of 30 min. The suspension was gradually brought to reflux, and allowed to stir for 16 h or until the solution turned clear yellow. Subsequently, the excess thionyl chloride and gaseous by-products were removed by vacuum transfer, while maintaining anhydrous conditions. The resulting yellow oil product, quantitative conversion by 1H-NMR and 13C-NMR, was used directly for further synthetic steps. 3,3'-dithiopropanoyl chloride: 1H-NMR (300 MHz, 303 K, CDCl3): delta=2.95 (t, 3JH-H=7.0 Hz, 4H), 3.32 (t, 3JH-H=7.0 Hz, 4H) ppm. 13C-NMR (300 MHz, 303 K, CDCl3): delta=32.00, 46.05, 172.09 ppm.
With thionyl chloride; In N,N-dimethyl-formamide; at 30℃; for 12h;Schlenk technique; Inert atmosphere; Step 1: A 100 mL schlenk tube was placed on a flame blower and dried under vacuum, followed by cooling under a nitrogen atmosphere.Then a stir bar and <strong>[1119-62-6]3,3'-dithiodipropionic acid</strong> (6.3 g, 30 mmol) were added under a nitrogen atmosphere.A solution of thionyl chloride (4.4 mL, 60 mmol) was quickly aspirated into a schlenk tube using a 5 ml syringe.To the reaction liquid, 6 drops (about 0.3 mL) of N,N-dimethylformamide was added dropwise as a catalyst to accelerate the progress of the reaction.The schlenk tube was placed in an oil bath, the temperature of the oil bath was controlled at 30 C, and stirring was vigorously for 12 hours.The reaction solution slowly changed from colorless to yellow.The reaction system is cooled to room temperature, and the volatile matter in the solution is removed by an oil pump in a vacuum environment.The dried crude product 3,3'-dithiodipropanoyl chloridewas obtained which was obtained without further purification.Can be used directly in the next reaction;
With thionyl chloride; N,N-dimethyl-formamide; at 30℃; for 12h;Schlenk technique; Inert atmosphere; Step 1: Select 100mL schlenk tube and place it on the flame blower.Dry the reaction tube under vacuum,The reaction tube was cooled under a nitrogen atmosphere. .Then a stir bar and 3,3'-dimercaptodipropionic acid (6.3 g, 30 mmol) were added under a nitrogen atmosphere.Draw with a 5 ml syringeDichlorosulfoxide(4.4 mL, 60 mmol) was quickly injected into the reaction solution, and 6 drops (about 0.3 mL) of N,N-dimethylformamide was added dropwise as a catalyst to accelerate the reaction. The reaction tube was placed in an oil bath, the oil bath was stably controlled at 30 C, and vigorously stirred for 12 hours, and the reaction solution was changed from colorless to yellow. The reaction system was cooled to room temperature, and the volatile matter in the solution was removed by an oil pump in a vacuum environment to obtain a dried crude product.3,3'-dimercaptodipropionyl chlorideThe product was used in the next step without further purification.
With thionyl chloride; N,N-dimethyl-formamide; In dichloromethane; General procedure: To a solution of 3,3?-disulfanediyldipropanoic acid 1b (1.0g, 4.76mmol) in DCM (20mL) in an ice bath was added dropwise thionyl chloride (1.24g, 10.46mmol) with a few drops of DMF as the catalyst. The solvent was removed in vacuo and the crude residue was further reacted with excess 4-chloroaniline (1.41g, 11.04mmol) in DCM. After 3h, the precipitate was filtered, washed with DCM, and dried in vacuo to yield the diamide compound as a white solid (1.82g) with sufficient purity for the next step. To a well-stirred solution of the diamide compound in DCM (25mL) was added 1.0 equiv. of SO2Cl2 (0.57g, 4.24mmol) in an ice bath. After 2h, the solution was poured into water and extracted with DCM. The organic layers were dried over anhydrous MgSO4, filtered and evaporated under reduced pressure. The resulting residue was purified by flash column chromatography on silica gel to afford the desired compound 5f (0.42g, 2.0mmol). Yield 47%; 1H NMR (400MHz, CDCl3) delta 8.19 (d, J=6.85Hz, 1H), 7.46-7.57 (m, 2H), 7.34-7.45 (m, J=8.80Hz, 2H), 6.29 (d, J=6.85Hz, 1H); 13C NMR (101MHz, CDCl3) delta 165.3, 146.6, 134.3, 133.4, 129.7, 125.9, 114.9; HRMS m/z calcd for [C9H6ClNOS+H]+ 211.9931, found 211.9926.
With oxalyl dichloride; In dichloromethane; N,N-dimethyl-formamide; at 0 - 20℃; for 3h;Inert atmosphere; 1.2. 3,3?-disulfanediyldipropionic acid (4 g, 0.019 mol, 1 eq.) was suspended in anhydrous DCM (100 mL) and anhydrous DMF (300 pL) was added, followed by oxalyl chloride (7.24 g, 0.057 mol, 3 eq.) at 0C under inert atmosphere. The solution clarified. The mixture was left for 3h at rt until it clarified and no gas formation was longer observed. The crude was evaporated and kept under reduced pressure for another 30 min to remove remnants of oxalyl chloride. A yellow oil (4.70 g, 100%) was obtained. The crude was used without further purification; Rg (in MeOH): 2.13; MS ES+ m/z: 206.86.

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  • 3
  • [ 1002-18-2 ]
  • [ 220339-96-8 ]
  • [ 220340-01-2 ]
YieldReaction ConditionsOperation in experiment
66% In tetrahydrofuran at 20℃; for 8h; Heating;
  • 4
  • [ 1002-18-2 ]
  • [ 5619-07-8 ]
  • 2-[3-[2-(1-methoxycarbonyl-2-phenyl-ethylcarbamoyl)-ethyldisulfanyl]propionylamino]-3-phenyl-propionic acid methyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
95% With triethylamine In dichloromethane; 1,2-dichloro-ethane at 5 - 15℃; for 4h;
  • 6
  • [ 67455-41-8 ]
  • [ 1002-18-2 ]
  • [ 748777-37-9 ]
  • 7
  • [ 1002-18-2 ]
  • [ 16154-70-4 ]
  • C32H44N6O6S2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
75.6% With sodium hydroxide In dichloromethane
  • 8
  • [ 1002-18-2 ]
  • [ 53297-68-0 ]
  • <i>N</i>-(2-chloro-4-sulfamoyl-phenyl)-3-[2-(2-chloro-4-sulfamoyl-phenylcarbamoyl)-ethyldisulfanyl]-propionamide [ No CAS ]
  • 9
  • [ 1002-18-2 ]
  • [ 654-70-6 ]
  • [ 1011526-76-3 ]
YieldReaction ConditionsOperation in experiment
94% In tetrahydrofuran; at 22 - 55℃; for 0.833333h; IA (10.0 g; 40.4 mmol; 1.0 equiv), neat, was added via syringe to a clear amber solution of 2-trifluoromethyl-4-aminobenzonitrile (14.9 g; 80.8 mmol; 2.0 equiv) in 80 mL dry THF at 22C. A slight exotherm was observed. The homogeneous amber solution was stirred for 20 min, and then placed in a 55C oil <n="57"/>bath for 30 min. HPLC indicated only a small amount of aniline was present. The contents of the reactor were concentrated in vacuo to yield a tan solid. After absorption onto silica, the crude material was purified by flash column chromatography (1% acetone/CH2Cl2 to elute aniline, then 10-50% acetone/CH2Cl2 to elute desired as a pale yellow band.) to give 20.3 g (94 %) of IB as an off-white solid. HPLC: 95% at 3.736 min (retention time) (YMC ODS-A column 4.6 x 50 mm eluting with 10-90% aqueous MeOH over 4 min containing 0.1% H3PO4, 4 mL/min, monitoring at 220 nm).
94% In tetrahydrofuran; at 22 - 55℃; for 0.833333h; To a clear amber solution of 2-trifluoromethyl 4-aminobenzonitrile (14.9 g; 80.8 mmol; 2.0 equiv) in 80 mL dry THF at 22C was added Compound IA (10.0 g; 40.4 mmol; 1.0 equiv), neat, by syringe. A slight exotherm was observed. The homogeneous amber solution stirred for 20 minutes, then placed in a 55C oil bath for 30 minutes. HPLC indicated only a small amount of aniline was present. The contents of the reactor were concentrated in vacuo, yielding a tan solid. After absorption onto silica, the crude material was purified by flash column chromatography (1% acetone/DCM to elute aniline, then 10-50% acetone/DCM to elute desired as a pale yellow band.) 20.3 g (94 %) of Compound IB was obtained as an off-white solid.[00153] 95% at 3.736 min (retention times) (YMC ODS-A column 4.6 x 50 mm eluting with 10-90% aqueous methanol over 4 minutes containing 0.1% H3PO4, 4 mL/min, monitoring at 220 nm).
  • 10
  • [ 40615-04-1 ]
  • [ 1002-18-2 ]
  • C12H9NOS2 [ No CAS ]
  • C12H8ClNOS2 [ No CAS ]
  • C12H8ClNOS2 [ No CAS ]
  • C12H7Cl2NOS2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
EXAMPLE 24 5-chloro-2-(3-chloro-benzo[b]thiophen-2-ylmethyl)-isothiazol-3-one (Cpd 6) 2-benzo[b]thiophen-2-ylmethyl-5-chloro-isothiazol-3-one (Cpd 7) 2-(3-chloro-benzo[b]thiophen-2-ylmethyl)-isothiazol-3-one (Cpd 8) 2-benzo[b]thiophen-2-ylmethyl-isothiazol-3-one (Cpd 9) Using the procedure of Example 1 and 2-benzo[b]thiophene methanamine Compound 24a (5.00 g, 30.6 mmol) in place of Compound 1c, elution with hexane:EtOAc 4:1 afforded Compound 6 as a tan solid. M.P. 118-120 C.; MS 338 (M+Na); 1H NMR (CDCl3) delta 6.29 (s, 1H), 5.21 (s, 2H). Further elution of the same column with hexane:EtOAc 1:1 gave Compound 7 and Compound 8. Compound 7 was obtained as a tan solid. M.P. 101-103 C.; MS 304 (M+Na); 1H NMR (CDCl3) delta 7.31 (s, 1H), 6.30 (s, 1H), 5.14 (s, 2H). Compound 8 was obtained as a tan solid. M.P. 139-142 C.; MS 282 (MH+); 1H NMR (CDCl3) delta 8.06 (d, 1H), 6.30 (d, 1H), 5.26 (s, 2H). Final elution with EtOAc gave Compound 9 as a tan solid. M.P. 144-146 C.; MS 270 (M+Na); 1H NMR (CDCl3) delta 8.07 (d, 1H), 6.30 (d, 1H), 5.19 (s, 2H).
  • 11
  • [ 1002-18-2 ]
  • [ 94341-56-7 ]
  • 5-chloro-2-(4-benzenesulfonyl-benzyl)-isothiazol-3-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
Compound 1b was then transferred via pipette to a second flask (cooled in an ice water bath) containing DCM (250 mL), 4-iodobenzylamine Compound 1c (5.50 grams, 0.024 mol) and TEA (3.3 mL, 0.024 mol). The reaction mixture was stirred for 3 hrs, then approximately 2 molar equivalents of sulfuryl chloride (4.00 mL, 0.050 mol) was added and the mixture was stirred at ambient temperature for an additional 3 hrs. The mixture was evaporated in vacuo and the resulting crude oil was dissolved in DCM (250 mL), washed with water, dried over magnesium sulfate and concentrated in vacuo. The crude product was chromatographed on a silica gel flash column using a mobile phase of hexane:EtOAc in a 2:1 ratio to afford the intermediate 4,5-dichloro-2-(4-iodo-benzyl)-isothiazol-3-one Compound 1d as a solid. M.P. 104.5-107 C.; 1H NMR (CDCl3) delta 7.71 (m, 2H), 7.07 (d, 2H), 4.89 (s, 2H). Using the procedure of Example 1 and Compound 16e in place of Compound 1c, Compound 38 was obtained. 1H NMR (CDCl3) delta 7.95 (d, 4H), 7.59-7.49 (m, 3H), 7.40 (m, 2H), 6.31 (s, 1H), 4.93 (s, 2H), MS 387.9 (M+H+).
  • 12
  • [ 1002-18-2 ]
  • [ 29840-56-0 ]
  • [ 1173531-62-8 ]
  • 13
  • [ 1002-18-2 ]
  • [ 93246-53-8 ]
  • [ 1213258-47-9 ]
  • 14
  • [ 1002-18-2 ]
  • [ 120-35-4 ]
  • C34H34N4O6S2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
0.937 g With N-ethyl-N,N-diisopropylamine; In dichloromethane; for 1.33333h;Inert atmosphere; (0189) Intermediate 4: 3,3'-Dithiopropionic acid (0.459 g, 2.18 mmol) was suspended in 20 mL EtOAc, and oxalyl chloride (0.58 mL, 6.65 mmol) was added under nitrogen, followed by DMF (0.05 mL). After 20 min the reaction was evaporated to an off-white film. This was redissolved in 15 mL dry DCM, and <strong>[120-35-4]3-amino-4-methoxybenzanilide</strong> (1.04 g, 4.3 mmol) was added, followed by N,N-diisopropylethylamine (DIEA) (0.78 mL, 4.49 mmol) and an additional 20 mL DCM. After 80 min the dense white slurry was filtered through a medium glass frit, rinsed with 2x20 mL DCM, 2x25 mL 1 M HCl, 2×25 mL 1 M NaOH, 2x50 mL water, and evaporated to dryness to yield the symmetrical disulfide, Intermediate 4, as an off-white solid (0.937 g, 65%). ES (+) MS m/e = 659 (M+1).
  • 15
  • [ 1002-18-2 ]
  • [ 7436-22-8 ]
  • C8H10(2)H6N2O2S2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Step 2: Weigh the <strong>[7436-22-8]methyl-d3-amine hydrochloride</strong> (201 mg, 3 mmol) with a balance.Place in a 25 mL round bottom flask and place the round bottom flask in an ice water bath.3 mL of 1 M sodium hydroxide was slowly added dropwise to the round bottom flask.Further, potassium carbonate (138 mg, 1 mmol) was weighed and poured into the reaction system to neutralize the acid formed in the reaction.The reaction system was continuously stirred in an ice water bath for about 20 minutes.After the completion of the stirring, the previously prepared 3,3'-dithiodipropionyl chloride (247 mg, 1 mmol) was weighed.It was slowly added dropwise to the reaction system at a rate of 3 mL/min in an ice water bath. If the addition rate was too fast, a large amount of by-products were formed to affect the product yield.After the completion of the dropwise addition, the reaction system was further stirred for 2 hours, at which time the reaction system was in a white suspension state.The water in the reaction system was removed by a rotary evaporator to obtain a white solid, and the solid at this time contained an inorganic salt such as sodium chloride.Add 5 mL of absolute ethanol and stir well to allow the organic matter to be sufficiently dissolved in ethanol, and the obtained suspension was filtered.The filter residue was washed twice with 10 mL of ethanol and filtered, the organic phases were combined, and the ethanol was dried with a rotary evaporator.The product deuterated amide is obtained as a white solid which is obtained without further purification.Can be used directly in the next reaction;
Step 2:4. The <strong>[7436-22-8]deuterated methylamine hydrochloride</strong> (201 mg, 3 mmol) was weighed out with a balance.Place in a 25 mL round bottom flask and place the round bottom flask in an ice water bath.3 mL of 1 M sodium hydroxide was slowly added dropwise to the flask.Further, potassium carbonate (138 mg, 1 mmol) was weighed and poured into the reaction system to neutralize the acid formed in the reaction, and the reaction system was continuously stirred in an ice water bath for about 20 minutes.After the completion of the stirring, the previously prepared 3,3'-dimercaptodipropionyl chloride (247 mg, 1 mmol) was weighed.It was slowly added dropwise to the reaction system at a rate of 3 mL/min in an ice water bath. If the addition rate was too fast, a large amount of by-products were formed to affect the product yield.After the completion of the dropwise addition, the reaction system was further stirred for 2 hours, at which time the reaction system became a white suspension. The water in the reaction system is removed by a rotary evaporator.A white solid was obtained, and the solid at this time contained an inorganic salt such as sodium chloride.Add 5 mL of ethanol and stir well to allow the organic matter to be fully dissolved in ethanol. The suspension was filtered, and the filter residue was washed twice with 10 mL of ethanol and filtered, and the organic phases were combined and the ethanol was spin-dried by a rotary evaporator. The product deuterated amide, the deuterated amide is a white solid, the product is obtained without further purification.Can be used directly in the next reaction.
  • 16
  • [ 1002-18-2 ]
  • [ 1394838-36-8 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
41% With triethylamine In dichloromethane at 20℃; Inert atmosphere; Cooling with ice; Synthesis of 2-(3,5-dichloro-2-fluorophenyl)isothiazol-3(2H)-one (ISFP5) 3,3'-Dithiodipropionic acid (1 g, 4.76 mmol) was placedunder an argon atmosphere in a dry round bottom ask(sealed with a turnover septum) and was dissolved in anhy-drous tetrahydrofuran (20 ml). The ask was then cooled on-ice followed by the dropwise addition of thionyl chloride(2.07 ml, 28.53 mmol) with stirring. N,N-dimethylformamide(74 μ l, 0.95 mmol) was then added to the stirring solution, andthe reaction was left to stir on ice for 20 min, at which pointthe ice was removed and the reaction was allowed to warm toroom temperature. The reaction was stirred at room temper-ature for a further 3 h at which point the ask was purged withargon and the solvent was carefully removed in vacuo using arotary evaporator (no heating). The resulting crude materialwas triturated twice using toluene followed by solvent removalin vacuo (no heating). The crude material was again dissolvedin tetrahydrofuran ( < 10 ml) and was evaporated to dryness invacuo (no heating). The crude material was subsequently usedwithout further puri cation.3,5-dichloro-2- uoroaniline (1 g, 5.5 mmol) was dissolved inanhydrous dichloromethane (5 ml) under an argon atmo-sphere. Triethylamine (6.95 mmol, 969 μ l) was then added tothe stirring solution and cooled on-ice. Separately, 3,30-disul-fanediyldipropionyl chloride from the rst reaction (344 mg,1.39 mmol) was suspended in anhydrous dichloromethane(5 ml) and was then added slowly to the stirring 3,5-dichloro-2- uoroaniline solution. The reaction was allowed to stir on-ice for 30 min, then warmed to room temperature, andallowed to stir overnight. The next day, a saturated aqueoussolution of sodium hydrogen carbonate (approx. 40 ml) wasadded slowly to the crude reaction mixture and the resultingsolution was extracted using dichloromethane (3 × 20 mlminimum). The organic phase was dried over sodium sulfate, ltered, and the solvent removed in vacuo (water bath at 35C). The crude material was dry loaded on silica and waspuri ed by ash chromatography (Heptane/Ethyl acetate (2:1)→ Ethyl acetate) (305 mg, 41% yield).The product, 3,30-disulfanediylbis(N-(3,5-dichloro-2- uorophenyl)propanamide) (210 mg, 0.39 mmol) was sus-pended (not dissolved) in anhydrous dichloromethane underan argon atmosphere and was cooled on-ice. A solution of1M sulfuryl chloride in dichloromethane ( 1 eq., 393 μ l) wasthen added to the stirring ask and was stirred for 15 min.Over the course of the following 1 to 2 h, an additional 4 to 5equivalents of sulfuryl chloride solution was added to thestirring solution until the solubility of the material in the ask improved. At this point, the reaction mixture wasallowed to warm to room temperature and stirred overnight.The next day, saturated brine solution (approx. 20 ml) was added to the off-white suspension followed by extractionwith ethyl acetate (3 × 20 ml minimum). The organic phasewas dried over sodium sulfate, ltered, and the solventremoved in vacuo (water bath at 30C) to the point wherethe solid crude product became visible in the ask. At thispoint, the reaction mixture was resolubilized with the mini-mum amount of solvent and was dry loaded onto silica for ash puri cation (Heptane/ethyl acetate (1:1) → ethyl ace-tate). The ash puri ed material then underwent a furtherpuri cation by reverse phase C18 HPLC (see supplementaryinformation for methods) (R f : 0.65; heptane/ethyl acetate,1:1) (19 mg, postlyophilisation, 18% yield).
41% With triethylamine In dichloromethane at 20℃; Inert atmosphere; Cooling with ice; Synthesis of 2-(3,5-dichloro-2-fluorophenyl)isothiazol-3(2H)-one (ISFP5) 3,3'-Dithiodipropionic acid (1 g, 4.76 mmol) was placedunder an argon atmosphere in a dry round bottom ask(sealed with a turnover septum) and was dissolved in anhy-drous tetrahydrofuran (20 ml). The ask was then cooled on-ice followed by the dropwise addition of thionyl chloride(2.07 ml, 28.53 mmol) with stirring. N,N-dimethylformamide(74 μ l, 0.95 mmol) was then added to the stirring solution, andthe reaction was left to stir on ice for 20 min, at which pointthe ice was removed and the reaction was allowed to warm toroom temperature. The reaction was stirred at room temper-ature for a further 3 h at which point the ask was purged withargon and the solvent was carefully removed in vacuo using arotary evaporator (no heating). The resulting crude materialwas triturated twice using toluene followed by solvent removalin vacuo (no heating). The crude material was again dissolvedin tetrahydrofuran ( < 10 ml) and was evaporated to dryness invacuo (no heating). The crude material was subsequently usedwithout further puri cation.3,5-dichloro-2- uoroaniline (1 g, 5.5 mmol) was dissolved inanhydrous dichloromethane (5 ml) under an argon atmo-sphere. Triethylamine (6.95 mmol, 969 μ l) was then added tothe stirring solution and cooled on-ice. Separately, 3,30-disul-fanediyldipropionyl chloride from the rst reaction (344 mg,1.39 mmol) was suspended in anhydrous dichloromethane(5 ml) and was then added slowly to the stirring 3,5-dichloro-2- uoroaniline solution. The reaction was allowed to stir on-ice for 30 min, then warmed to room temperature, andallowed to stir overnight. The next day, a saturated aqueoussolution of sodium hydrogen carbonate (approx. 40 ml) wasadded slowly to the crude reaction mixture and the resultingsolution was extracted using dichloromethane (3 × 20 mlminimum). The organic phase was dried over sodium sulfate, ltered, and the solvent removed in vacuo (water bath at 35C). The crude material was dry loaded on silica and waspuri ed by ash chromatography (Heptane/Ethyl acetate (2:1)→ Ethyl acetate) (305 mg, 41% yield).The product, 3,30-disulfanediylbis(N-(3,5-dichloro-2- uorophenyl)propanamide) (210 mg, 0.39 mmol) was sus-pended (not dissolved) in anhydrous dichloromethane underan argon atmosphere and was cooled on-ice. A solution of1M sulfuryl chloride in dichloromethane ( 1 eq., 393 μ l) wasthen added to the stirring ask and was stirred for 15 min.Over the course of the following 1 to 2 h, an additional 4 to 5equivalents of sulfuryl chloride solution was added to thestirring solution until the solubility of the material in the ask improved. At this point, the reaction mixture wasallowed to warm to room temperature and stirred overnight.The next day, saturated brine solution (approx. 20 ml) was added to the off-white suspension followed by extractionwith ethyl acetate (3 × 20 ml minimum). The organic phasewas dried over sodium sulfate, ltered, and the solventremoved in vacuo (water bath at 30C) to the point wherethe solid crude product became visible in the ask. At thispoint, the reaction mixture was resolubilized with the mini-mum amount of solvent and was dry loaded onto silica for ash puri cation (Heptane/ethyl acetate (1:1) → ethyl ace-tate). The ash puri ed material then underwent a furtherpuri cation by reverse phase C18 HPLC (see supplementaryinformation for methods) (R f : 0.65; heptane/ethyl acetate,1:1) (19 mg, postlyophilisation, 18% yield).
Same Skeleton Products
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