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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. : | 13939-06-5 |
Formula : | C6MoO6 |
M.W : | 264.00 |
SMILES Code : | [C]=O.[C]=O.[C]=O.[C]=O.[C]=O.[C]=O.[Mo] |
MDL No. : | MFCD00003466 |
GHS Pictogram: |
![]() |
Signal Word: | Danger |
Hazard Statements: | H300+H310+H330 |
Precautionary Statements: | P262-P264-P270-P271-P280-P284-P302+P350-P304+P340-P310-P330-P361-P363-P403+P233-P405-P501 |
Class: | 6.1 |
UN#: | 3466 |
Packing Group: | Ⅱ |
* 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 |
---|---|---|
With 1,8-diazabicyclo[5.4.0]undec-7-ene;palladium diacetate; In 1,4-dioxane; at 120℃; for 0.333333h;Sealed tube; Microwave irradiation; | A 5 mL microwave vial was charged with l-bromo-3-iodo-5-(trifluoromethoxy)benzene(98 mg, 0.27 mmol), <strong>[56622-54-9](6-methylpyridin-3-yl)methanamine</strong> (50 mg, 0.41 mmol), molybdenum hexacarbonyl (160 mg, 0.61 mmol), palladium acetate (8 mg, 0.036 mmol), l,8-diazabicyclo[5.4.0]undec- 7-ene (120 mg, 0.79 mmol), and 1,4-dioxane (2 mL). The vial was sealed under nitrogen and the reaction was subjected to microwave irradiation at 120 0C for 20 minutes. After cooling, the mixture was purified via flash chromatography to afford the desired product as a white solid. LC-MS: 391.2 [M+l]+; 1H NMR (CDCl3, 400 MHz): 8.43 (d, J = 2.1 Hz, IH), 7.85 (t, J = 1.5 Hz, IH), 7.63-7.61 (m, 2H), 7.52 (s, IH), 7.16 (d, J = 8.0 Hz, IH), 6.74 (br, IH), 4.60 (d, J = 5.8 Hz, 2H), 2.55 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | trans-di(mu-acetato)bis[o-(di-o-tolylphosphino)benzyl]dipalladium(II); tri tert-butylphosphoniumtetrafluoroborate; In tetrahydrofuran; at 125℃; for 0.166667h; | To N-[(7i?, 2S)- 1 - { [ 1 -(3-bromophenyl)- 1 eta-indazol-5-yl]oxy } - 1 -(6-methoxypyridin-3- yl)propan-2-yl]-2,2-difluoropropanamide (37 mg, 68mumol), <strong>[88675-24-5]3-aminotetrahydrofuran</strong> (18 mg, 204mumol), tri-t-butylphosphoniumtetrafluoroborat (8.8 mg, 31 mumol) and trans- bis(acetato)bis[o-(di-o-tolylphosphino)-benzyl]dipalladium(II) (10.3 mg, 14mumol) in 1.5 mL THF was added molybdaenhexacarbonyl (12.5 mg, 47 mumol). The microwave vessel was closed and radiated in a microwave reactor (CEM discover) at 150 W and 125°C for 10 minutes (5 minutes ramp time. Then the solvent was removed i.vac, and the product purified by preparative thin layer chromatography on silica gel (ethyl acetate 100percent) to <n="57"/>yield 11 mg (30percent) 3-(5-[(7i?,25)-2-[(2,2-difluoropropanoyl)amino]-l-(6- methoxypyridin-3 -yl)propyl]oxy } - 1 H-indazol- 1 -y l)-N-(tetrahydrofuran-3 -yl)benzamide . ES+MS: m/z 580 [MH+]1H-NMR (300 MHz, CDCl3); delta = 8.20 (d, IH), 8.08 (dd, IH), 8.02 (s, IH), 7.83 (m, IH), 5 7.71 (m, IH), 7.67 (d, IH), 7.60 (dd, IH), 7.58 (t, IH), 7.16 (dd, IH), 6.99 (d, IH), 6.76 (d, IH), 6.66 (br, IH), 6.43 (br, IH), 5.36 (d, IH), 4.75 (m, IH), 4.40 (dq, IH), 4.01 (m,lH), 3.92 (s, 3H), 3.91 (m, IH), 3.83 (m, 2H), 2.38 (m, IH), 1.95 (m, IH), 1.77 (t, 3H), 1.29 (d, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With dmap; 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; water; at 120℃; for 5h;Inert atmosphere; Sealed tube; | Example 109 - Preparation of Intermediate 36 The synthesis of Intermediate 36 followed the procedure of General Procedure 24 following: Intermediate 35 Intermediate 36 To a stirred solution of tert-butyl-3-(trifluoromethylsulfonyloxy)-8- azabicyclo[3.2.1]oct-3-ene-8-carboxylate (Intermediate 35, 21 g, 58.8 mmol) in 1,4- dioxane:water (5:1, 125 mL) in a sealed tube was added molybdenum hexacarbonyl (Mo(CO)6, 7.7 g, 29.4 mmol), 4-dimethylaminopyridine (DMAP, 14.3 g, 117.6 mmol), and N,N-diisopropylethylamine (DIEA, 25 mL, 141.2 mmol). After degassing with a stream of argon for 15 minutes, palladium acetate (Pd(OAc)2, 1.3 g, 5.9 mmol) was added, followed by 1,1'-bis(diphenylphosphino)ferrocene (dppf, 3.3 g, 5.9 mmol). The reaction mixture was stirred at 120C for 5 hours. The reaction mixture was filtered through a Celite pad and poured into aqueous sodium bicarbonate (60 mL) and extracted with EtOAc (200 mL). The aqueous layer was acidified with HCl (2N, to pH = 2) and extracted with EtOAc (2 x 200 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure to afford 8-(tert-butoxycarbonyl)-8-azabicyclo[3.2.1]oct-3-ene-3-carboxylic acid (Intermediate 36, 14 g, yield: 94%) as a light brown liquid; TLC System: 50% ethyl acetate in hexane. Rf-0.2. |
With dmap; N-ethyl-N,N-diisopropylamine;1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; In 1,4-dioxane; water; at 150℃; for 0.166667h;Microwave irradiation; | 8.1/ 8-Azabicyclo[3.2.1]oct-2-ene-3,8-dicarboxylic acid 8-tert-butyl ester 3-Trifluoromethanesulfonyloxy-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylic acid tert-butyl ester (2.0 g, 5.6 mmol), hexacarbonylmolybdenum (0.74 g, 2.8 mmol), palladium diacetate (0.13 g, 0.56 mmol), 1,1'-bis(diphenylphosphino)ferrocene (0.31 g, 0.56 mmol), 4-dimethylaminopyridine (1.37 g, 11.2 mmol) and diisopropyl-ethylamine (2.24 ml, 12.9 mmol) are placed in 2.0 ml of water and 12 ml of dioxane in a microwave reaction vessel. The medium is microwave-heated at 150 C. for 10 min. The crude product is taken up with water and with dichloromethane. The organic phase is extracted with a saturated aqueous NaHCO3 solution. The aqueous phase is acidified with KHSO4 and then extracted with ethyl acetate. The organic phase is washed with water and then with a saturated aqueous sodium chloride solution and dried over MgSO4. After concentrating to dryness, 2.7 g of expected 8-aza-bicyclo[3.2.1]oct-2-ene-3,8-dicarboxylic acid 8-tert-butyl ester are obtained. [M+H+]=253 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | In a glovebox under argon, to chamber 1 of two- chamber system S2 was added Pd(dba)2 (19.9 mg, 0.0347 mmol), PPh3 (18.2 mg, 0.0693 mmol), 4,6-dichloro-2-iodo-3-methoxyphenol 37 (221 mg, 0.693 mmol), THF (3 ml_), (S)-(l-ethylpyrrolidin-2-yl)methanamine (193 muIota_, 1.39 mmol), TEA (194 muIota_, 1.39 mmol). The chamber was sealed with a screwcap fitted with a Teflon.(R). seal. In a glovebox under argon, to chamber 2 of two-chamber system S2 was added Mo(CO)6 (183 mg, 0.693 mmol), THF (3 ml_) and pyridine (280 muIota_, 3.47 mmol) in that order. The chamber was sealed with a screwcap fitted with a Teflon.(R). seal. The loaded two-chamber system was heated to 70 °C for 19 hours. The crude reaction mixture was evaporated on silica gel and the title compound 38 was obtained after flash chromatography (5percent MeOH in CH2CI2 as eluent) as brown oil (153.7 mg, 0.443 mmol, 64percent from 37). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With C35H20F34NO3(1-)*Pd(2+)*Cl(1-); N-ethyl-N,N-diisopropylamine; In neat (no solvent); at 130℃; for 0.283333h;Microwave irradiation; | General procedure: A mixture of the aryl halide (1.0 mmol), alcohol (5.0 equiv), Mo(CO)6 (0.5 equiv), DIPEA (1.5 equiv) and palladacycle 1 (1 mol % Pd) was heated in a pressure tube at 130 C under microwave irradiation. The reaction was monitored by TLC. When the reaction has completed, the reaction mixture was cooled to room temperature and the alcohol was removed. The crude mixture was subjected to F-SPE to remove palladacycle 1 (see general procedure for the recycling of palladacycle 1) and the solution of crude product was concentrated, diluted with EtOAc (20 mL) and washed successively with 2 M HCl (210 mL) and water (10 mL). The organic layer was driedover anhydrous MgSO4, filtered and concentrated to give pure 6. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With tetraethylammonium bromide; 1,8-diazabicyclo[5.4.0]undec-7-ene; In 1,4-dioxane; at 20 - 110℃; for 1h; | General procedure: To a screw cap vial was added osylhydrazone (1.0 mmol) in 1,4 Dioxane (5.0 mL). Thencharged etraethylammonium bromide (1.0 mmol) followed by the addition of DBU (2.5 mmol)and Mo(CO)6 (1.0 mmol) at room temperature. The mixture was heated to 110"C for 1.0 h. Thereaction progress was monitored by using TLC. After consumption of starting material thereaction mixture was filtered through celite bed and washed with ethyl acetate. The ethyl acetatelayer was washed with water and brine. The organic phase was dried over sodium sulphate,filtered and concentrated under reduced pressure to afford crude compound. The crudecompound was purified by flash column chromatography on Biotage instrument using 4.0 g snapcartridge and eluted with ethyl acetate in hexane to give oxindole. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
29% | With copper diacetate; palladium diacetate; 1,8-diazabicyclo[5.4.0]undec-7-ene; In 1,4-dioxane; at 95℃; | General procedure: The reaction was performed in a double-chamber system [67,68]. Amine/amines, Pd(OAc)2(0.05 equiv.) and Cu(OAc)2 (0.5 equiv.) were added to the reaction chamber and dissolved in1,4-dioxane (2 mL). In the CO-chamber was Mo(CO)6 (200 mg) dissolved in 1,4-dioxane (2 mL).After capping of the system, 1,8-diazabicyclo[5.4.0]undec-7-ene was added to the CO-chamber.The double-chamber system was positioned in a Dry-Syn heating block and heated to 95 C. Aftercompletion of the reaction, the reaction mixture was filtered through a short silica plug before flashcolumn chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
12% | With copper diacetate; palladium diacetate; 1,8-diazabicyclo[5.4.0]undec-7-ene; In 1,4-dioxane; at 95℃; | General procedure: The reaction was performed in a double-chamber system [67,68]. Amine/amines, Pd(OAc)2(0.05 equiv.) and Cu(OAc)2 (0.5 equiv.) were added to the reaction chamber and dissolved in1,4-dioxane (2 mL). In the CO-chamber was Mo(CO)6 (200 mg) dissolved in 1,4-dioxane (2 mL).After capping of the system, 1,8-diazabicyclo[5.4.0]undec-7-ene was added to the CO-chamber.The double-chamber system was positioned in a Dry-Syn heating block and heated to 95 C. Aftercompletion of the reaction, the reaction mixture was filtered through a short silica plug before flashcolumn chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With dmap; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; 1,8-diazabicyclo[5.4.0]undec-7-ene; triethylamine; In 1,4-dioxane; at 85℃;Sealed tube; Microwave irradiation; | General procedure: To a solution of compound77(0.40g, 1.35mmol) in dioxane (2mL) were added indoline (0.3mL, 2.70mmol), triethylamine (0.37mL, 2.70mmol), and 4-dimethylaminopyridine (0.16g, 1.35mmol). The mixture was purged with nitrogen for 2min. ThenPd (dppf)Cl2.CH2Cl2 (0.11g, 0.14mmol) and Mo(CO)6(0.18g, 0.68mmol) were added and the mixture was sealed in a microwave tube and heated to 85C overnight.The reaction was monitored by TLC. Upon completion, the reaction was cooled to room temperature, and diluted with water, and extracted with EtOAc (3*20mL). The combined organic fractions were washed with brine, dried over Na2SO4, and concentrated by evaporation under reduced pressure. Purification by silica gel column chromatography (gradient elution, gradient 0 to 25% EtOAc/60-90C petroleum ether) gave compound43as a light red solid (0.38g, 1.05mmol, 78% yield). |
Tags: Hexacarbonylmolybdenum | Molybdenum | Transition Metal | Transition Metals | 13939-06-5
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H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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