Structure of 183723-09-3
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CAS No. : | 183723-09-3 |
Formula : | C8H8BrNO |
M.W : | 214.06 |
SMILES Code : | O=C(N)C1=CC=C(C)C(Br)=C1 |
MDL No. : | MFCD03306087 |
InChI Key : | HAUIONXDUJDQSK-UHFFFAOYSA-N |
Pubchem ID : | 681061 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P301+P312-P302+P352-P304+P340-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 |
---|---|---|
With Rhodococcus rhodochrous ATCC BAA 870 cobalt nitrile hydratase; In aq. buffer; at 30℃;pH 7.6;Enzymatic reaction; | General procedure: 1800 muL (90%) Tris buffer (50 mM, pH 7.6) and 200 muL(10%) of methanol or acetone. In a 2 mL Eppendorf, NHase (10 mg) was added followed by Trisbuffer. Nitrile substrate (10 mg dissolved in 200 muL methanol or acetone) was added to the 2 mLEppendorf tube. (If an amine group was present on the nitrile substrate a Tris buffer of pH 9 wasused). The reaction mixture was incubated at 30 C on an ESCO Provocell microplateshaker/incubator (Esco Technologies, Halfway House, South Africa) (199 rpm). The reaction wasallowed to proceed for 24 h, 48 h or 5 d, depending on conversion, as monitored by TLC analysis.Ethyl acetate and water were added to the reaction mixture, and after separation, the organic layerwas concentrated under reduced pressure, and the resulting mixture was then purified by silica gelcolumn chromatography eluting with 20% to 90% ethyl acetate/ hexane. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With thionyl chloride; at 85℃; for 6h; | Intermediate 43; 3-Bromo-4-methyl-benzonitrile; 3-Bromo-4-methyl-benzoic acid (3g) in toluene (75ml) was treated with oxalyl chloride (1 OmI) and DMF (4 drops). The mixture was then stirred at 2OC for 3h. and then the solvent evaporated giving a yellow solid. This in turn was dissolved in THF (30ml) containing N-methyl-morpholine (1.5ml). Aqueous ammonia (0.880, 40ml) was then added and the mixture stirred for 18h. The THF was then evaporated and the resulting amide intermediate collected by filtration as a colourless solid (2.9g). This material was then suspended in thionyl chloride (35ml) and was heated to 85C for 6h. The excess reagent was then evaporated and the residue purified on silica gel. Elution with 5-50% ethyl acetate in hexane gave the title compound as a white solid (1.4g) | |
With 1,3,5-trichloro-2,4,6-triazine; at 0 - 20℃; | General procedure: To 2-bromo-3-methylbenzoic acid (21, 159 g, 739 mmol) in dichloromethane (1000 mL) was added triethylamine (TEA, 119.7 mL, 813 mmol, 1.1 equiv) followed by iso-butyl chloroformate (101.5 mL, 813 mmol, 1.1 equiv) in dichloromethane (DCM, 200 mL) at 0 C over 10 min. Concentrated ammonia water (323 mL) was then added at 0 C over 2 min. The reaction mixture was poured into water (200 mL), cooled to rt and filtered. The solid was washed with water (2 × 300 mL), 0.5 N HCl (2 × 150 mL) and dried to give the amide as a solid (120 g, yield 76%). To the solution of the amide obtained (50 g, 233.6 mmol) in DMF (300 mL) was added 2,4,6-trichloro-1,3,5-triazine (64.6 g, 350.4 mmol, 1.5 equiv) dropwise at 0 C and the reaction was stirred at rt overnight. To the reaction was added 600 mL of water and the reaction was stirred for 30 min. All insoluble was removed by filtration and the solid was triturated with ethyl acetate (EA, 3 × 100 mL) for 40 min and filtered. The filtrate was washed with saturated sodium carbonate (3 × 200 mL), saturated sodium chloride (200 mL) and dried over anhydrous sodium sulfate.The solvent was removed under reduced pressure to give 22 as a solid (42 g, yield 87.3%). To a solution of 22 (20 g, 102.2 mmol, 1 equiv) in CCl4 (200 mL) was added NBS (18.2 g, 102.0 mmol, 1.0 equiv), Bz2O2 (0.15 g, 0.6 mmol, 0.006 equiv). The reaction was refluxed overnight under N2, cooled and filtered. The filtrate was crystallized at 0 C to provide the brominated intermediate (15 g, yield 53.6%). To a solution of the brominated intermediate (90 g, 327.3 mmol) in DMF (760 ml) was added KOAc (38.6 g, 393.1 mmol, 1.2 equiv). The reaction mixture was stirred at 80 C for 1 h, cooled and water (1 L) was added. The mixture was extracted with EA (1 L). The organic layer was washed with 0.5 N HCl (3 ×200 mL), 2% NaHCO3 (200 mL) and dried over anhydrous sodium sulfate. The solvent was removed to give 23 as a yellow solid (77.3 g, yield 92.9%). 1H NMR of 23 (500 MHz, CDCl3): delta 2.16 (s, 3H), 5.21 (s, 2H), 7.43-7.46 (t, 1H,), 7.63 (m, 2H) ppm. To a solution of 23 (20 g, 78.8 mmol) in 1,4-dioxane (400 mL) was added bis(pinacolato)diboron (30 g, 118.1 mmol, 1.5 equiv) and KOAc (33.2 g, 338.1 mmol, 4.3 equiv). After being de-gassed and backfilled with nitrogen, Pd(dppf)Cl2 (3.2 g, 3.935 mmol, 0.05 equiv) was added. The reaction was refluxed overnight under nitrogen, cooled and filtered. The filtrate was concentrated and the residue was purified by silica gel column chromatography eluted with petroleum ether (PE)/EA = 5:1 to give 24 as red oil (29 g, crude yield 100% with 80% purity). 1H NMR of 24 (500 MHz, DMSO-d6): delta 1.42 (s, 12H), 2.20 (s, 3H), 5.25 (s, 2H), 7.44-7.49 (t, 1H), 7.57-7.64 (m, 2H) ppm. To a solution of 24 (29 g) in MeOH (100 mL) was added a solution of NaOH in MeOH (7.0 g/130 mL, 175.8 mmol, 2.3 equiv) and the reaction was stirred for 2 h at rt. The reaction mixture was concentrated under vacuum and the residue was dissolved in THF (150 mL) and 2 N HCl (138 mL, 69 mmol, 0.9 equiv). The reaction was stirred at rt for 50 min, concentrated and filtered. The solid was washed with water (3 × 20 mL) and petroleum ether (3 × 20 mL) to provide 25 (7.6 g, yield 62%). 1H NMR of 25 (500 MHz, DMSO-d6): delta 5.05 (s, 2H), 7.63-7.68 (t, 1H), 7.73-7.81 (m, 2H) ppm. To Raney Ni (0.849 g, 14.5 mmol, 2.3 equiv) in formic acid (10 mL) and water (2 mL) was added 25 (1 g, 6.29 mmol) at rt. The reaction was stirred at 100 C for 1 h, cooled and then filtered. The solvent was removed to give a solid that was purified by silica gel column chromatography eluted with CH2Cl2 to give 26 as a solid (0.714 g, yield 70%). 1H NMR of 26 (500 MHz, CDCl3): delta 10.03 (s, 1H), 8.08 (s, 1H), 7.86 (t, 1H), 7.63-7.71 (m, 2H), 5.20 (s, 2H) ppm. To a mixture of HCOOH (116.2 g, 10.0 equiv) and TEA (102.2 g, 4.0 equiv) were added 26 (40.9 g, 252.5 mmol) and 2,2-dimethyl-1,3-dioxane-4,6-dione (43.7 g, 1.2 equiv). The resulting mixture was refluxed for 15 h and cooled to rt. Hydrochloric acid (2 N, 320 mL) was added into the mixture that was then extracted with ethyl acetate twice (2 × 250 mL). The combined organic layer was washed with 2 N HCl (160 mL) and rotary evaporated to give the crude product that was recrystallized from DMF and 2 N HCl (34:204 mL) providing compound 1 as a white solid (15.6 g, yield 30%). An additional recrystallization from DMF and 2 N HCl (16:96 mL) was performed to give high purity product (12.9 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44% | With copper(l) iodide; (1R,2R)-1,2-diaminocyclohexane; potassium carbonate; In 1,4-dioxane; at 120℃; for 12h; | To a solution of 3-bromo-4-methylbenzamide (78.30 mg, 365.80 pmol) in dioxane (2 mL) were added <strong>[55512-82-8]3-bromoisothiazole</strong> (50 mg, 304.83 pmol), Cul (11.61 mg, 60.97 pmol), (li?,2i?)-cyclohexane-l,2-diamine (6.96 mg, 60.97 pmol) and K2CO3 (84.26 mg, 609.67 pmol). The reaction mixture was stirred at 120C for 12 hours, then poured into water extracted with EtOAc. The organic layer was washed with brine, dried over Na2S04, and concentrated under reduce pressure. The crude product was purified by column chromatography (S1O2) eluting with a gradient of 5-10% EtOAc in petroleum ether to give the title compound as a yellow solid (40 mg, 44%). NMR (400 MHz, DMSO-Tis) d ppm 2.43 (s, 3 H) 7.51 (d, 7=8.0 Hz, 1 H) 7.87 (d, 7=4.8 Hz, 1 H) 7.96 (dd, Ji = 8.0, J2 = 2.0 Hz, 1 H) 8.18 - 8.38 (m, 1 H) 9.07 (d, 7=4.8 Hz, 1 H) 11.55 (s, 1 H); ESI-MS m/z [M+H]+ =297.0. |
Tags: 183723-09-3 synthesis path| 183723-09-3 SDS| 183723-09-3 COA| 183723-09-3 purity| 183723-09-3 application| 183723-09-3 NMR| 183723-09-3 COA| 183723-09-3 structure
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