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Chemical Structure| 1250939-12-8 Chemical Structure| 1250939-12-8

Structure of 1250939-12-8

Chemical Structure| 1250939-12-8

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Product Details of [ 1250939-12-8 ]

CAS No. :1250939-12-8
Formula : C19H24BrNO5
M.W : 426.30
SMILES Code : O=C(N1[C@H](C(OCC(C2=CC=C(Br)C=C2)=O)=O)CC[C@@H]1C)OC(C)(C)C

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Application In Synthesis of [ 1250939-12-8 ]

* 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 [ 1250939-12-8 ]

[ 1250939-12-8 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 334769-80-1 ]
  • [ 99-73-0 ]
  • [ 1250939-12-8 ]
YieldReaction ConditionsOperation in experiment
52% With triethylamine; In dichloromethane; at 0 - 25℃; for 3.5h; [001691 To a cooled 0°C solution of compound 1-6 (5.0 g, 21.8 mmol) and compound 1-6-2 (7.28 g, 26.17 mmol) in DCM (140 mL) was added TEA (4.54 mL, 32.7 mmol) dropwise. The mixture was stirred at 25 °C for 3.5 hours. After the reaction was completed, the mixture was quenched with H20 (80 mL) and extracted with DCM (100 mLx3). The combined organic phases were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by silica gel column chromatography (PE/EtOAc (v/v) = 5/1) to give the title compound as a white solid (4.73 g, 52percent). The compound was characterized by the following spectroscopic data:MS (ESI, pos.ion) m/z: 426.3 [M+Hfb; and?H NMR (400 MHz, CDC13): 7.78-7.75 (m, 2H), 7.65-7.63 (m, 2H), 5.53-5.15 (m, 2H), 4.49-4.39 (m, 1H), 3.59-3.54 (m, 1H), 2.31-2.21 (m, 2H), 2.12-2.01 (m, 1H), 1.98-1.85 (m, 1H), 1.45 (s, 9H), 1.12-1.13 (d,J= 6.4 Hz, 3H) ppm.
52% With triethylamine; In dichloromethane; at 0 - 25℃; for 3.5h; Step 9) the Preparation of Compound 1-12 (0243) To a cooled 0° C. solution of compound 1-6 (5.0 g, 21.8 mmol) and compound 1-6-2 (7.28 g, 26.17 mmol) in DCM (140 mL) was added TEA (4.54 mL, 32.7 mmol) dropwise. The mixture was stirred at 25° C. for 3.5 hours. After the reaction was completed, the mixture was quenched with H2O (80 mL) and extracted with DCM (100 mL×3). The combined organic phases were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by silica gel column chromatography (PE/EtOAc (v/v)=5/1) to give the title compound as a white solid (4.73 g, 52percent). The compound was characterized by the following spectroscopic data: (0244) MS (ESI, pos. ion) m/z: 426.3 [M+H]+; and (0245) 1H NMR (400 MHz, CDCl3): delta 7.78-7.75 (m, 2H), 7.65-7.63 (m, 2H), 5.53-5.15 (m, 2H), 4.49-4.39 (m, 1H), 3.59-3.54 (m, 1H), 2.31-2.21 (m, 2H), 2.12-2.01 (m, 1H), 1.98-1.85 (m, 1H), 1.45 (s, 9H), 1.12-1.13 (d, J=6.4 Hz, 3H) ppm.
With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 20℃; for 5h; Example M10, Step cTo a solution of acid MlOb (2.16 g, 9.42 mmol) and 2-bromo-l-(4- bromophenyl)ethanone (2.62 g, 9.42 mmol) in acetonitrile (50 mL) was added slowly diisopropylethylamine (1.645 mL, 9.42 mmol), and the reaction mixture was stirred at room temperature for 5 hr. Solvent was removed in vacuo, and the residue was partitioned between ethyl acetate and water (1 : 1, 100 mL). The organic layer was washed with sat. aHC03, dried ( a2S04) and concentrated in vacuo to afford ketoester MlOc as white solid (3.9g), which was used in the next step without further purification. XH NMR (400 MHz , DMSO-d6, delta = 2.5 ppm): 7.92 (d, J = 8.3, 2H), 7.78 (d, J = 8.5, 2H), 5.6-5.4 (m, 2H), 4.35 (m, 1H), 3.85 (m, 1H), 2.25 (m, 1H), 2.05 (m, 2H), 1.60 (m, 1H), 1.5/1.4 (two overlapping br s, 9H), 1.18 (d, J = 6.6, 3H). LC/MS: Anal. Calcd. for [M+Na Ci9H2481BrNaN05: 450.07; found: 450.00.
With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 20℃; for 16h; To a solution of 2-bromo- 1 -(4-bromophenyl)ethanone (2.425 g, 8.72 mmol) and (2S,5S)-l-(tert-butoxycarbonyl)-5-methylpyrrolidine-2-carboxylic acid (2 g, 8.72 mmol) in acetonitrile (50 mL) was added DIEA (1.524 mL, 8.72 mmol), and the mixture was stirred at room temperature for 16 hrs. Solvent was removed in vacuo and the residue was partitioned between EtOAc (40 mL) and water (30 mL). The organic phase was washed with sat. NaHCCh and brine, and dried with a2S04. Removal of the volatile component in vacuo afforded Example 4, step d (1.74 g) as light yellow solid, which was used without further purification. 1H NMR (DMSO-d6, delta = 2.5 ppm, 400 MHz): 7.95-7.90 (m, 2H), 7.81 (m, 1H), 7.79 (m, 1H), 5.63-5.44 (m, 2H), 4.36 (m, 1H), 3.99 (m, 1H), 2.27 (m, 1H), 2.09 (m, 2H), 1.63 (m, 1H), 1.41- 1.37 (two singlet, 9H), 1.19 (m, 3H). LC/MS: Anal. Calcd. for [M+Na]+ Ci9H24BrNNa05: 448.07; found: 448.06.
With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 20℃; for 16h; Exam le QC-18.1, step dTo a solution of 2-bromo- 1 -(4-bromophenyl)ethanone (2.425 g, 8.72 mmol) and (2S,5S)-l-(tert-butoxycarbonyl)-5-methylpyrrolidine-2-carboxylic acid (2 g, 8.72 mmol) in acetonitrile (50 mL) was added DIEA (1.524 mL, 8.72 mmol), and the mixture was stirred at room temperature for 16 hrs. Solvent was removed in vacuo and the residue was partitioned between EtOAc (40 mL) and water (30 mL). The organic phase was washed with sat. aHC03 and brine, and dried with Na2S04. Removal of the volatile component in vacuo afforded Example 18.1, step d (1.74 g) as light yellow solid, which was used without further purification. lH NMR (DMSO- d6, delta = 2.5 ppm, 400 MHz): 7.95-7.90 (m, 2H), 7.81 (m, 1H), 7.79 (m, 1H), 5.63-5.44 (m, 2H), 4.36 (m, 1H), 3.99 (m, 1H), 2.27 (m, 1H), 2.09 (m, 2H), 1.63 (m, 1H), 1.41- 1.37 (two singlet, 9H), 1.19 (m, 3H). LC/MS: Anal. Calcd. for [M+NafCi9H24Br a05: 448.07; found: 448.06.
With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 20℃; for 2h;Inert atmosphere; (a) (2S,5S)-5-Methyl-pyrrolidine-1,2-dicarboxylic acid 2-[2-(4-bromo-phenyl)-2-oxo-ethyl]ester 1-tert-butyl ester A mixture of the product of Preparation 41 (1.7 g, 7.41 mmol), 2-bromo-1-(4-bromo-phenyl)-ethanone (2.08 g, 7.49 mmol) and DIPEA (2.87 g, 22.23 mmol) in ACN (50 mL) was stirred under nitrogen at RT for 2 h. The reaction mixture was concentrated under reduced pressure to give the title intermediate (3.16 g).
In acetonitrile; at 20℃; for 5h;Inert atmosphere; General procedure: 2, 4'-Dibromoacetophenone (24 g, 87 mmol) was added under N2 at room temperature to a solution of compound BB2-d (154 g, 87 mmol) in MeCN (100 ml) followed by slow addition of DIEA (34 g, 261 mmol). The mixture was stirred at rt for 5 h then concentrated in vacuo and the resulting residue was diluted with EtOAc, washed with 1 N HCI (2x50 ml), saturated NaHC03 (2x50 ml) and brine (2x50 ml), dried over anhydrous Na2S04, filtered and concentrated. The residue was purified by column chromatography (p.ether/EtOAc 10: 1) which gave the title compound (27 g, 84percent). MS (ESI): 369 [M+H]+.
1.74 g With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 20℃; for 16h; To a solution of 2-bromo- 1 -(4-bromophenyl)ethanone (2.425 g, 8.72 mmol) and (2S,5S)-l-(tert-butoxycarbonyl)-5-methylpyrrolidine-2-carboxylic acid (2 g, 8.72 mmol) in acetonitrile (50 mL) was added DIEA (1.524 mL, 8.72 mmol), and the mixture was stirred at room temperature for 16 h. Solvent was removed in vacuo and the residue was partitioned between EtOAc (40 mL) and water (30 mL). The organic phase was washed with sat. aHC03 and brine, and dried with Na2S04. Removal of the volatile component in vacuo afforded Example 18.1, step d (1.74 g) as light yellow solid, which was used without further purification. 1H NMR (DMSO-d6, delta = 2.5 ppm, 400 MHz): 7.95-7.90 (m, 2H), 7.81 (m, 1H), 7.79 (m, 1H), 5.63-5.44 (m, 2H), 4.36 (m, 1H), 3.99 (m, 1H), 2.27 (m, 1H), 2.09 (m, 2H), 1.63 (m, 1H), 1.41-1.37 (two singlet, 9H), 1.19 (m, 3H). LC/MS: Anal. Calcd. for [M+Naf Ci9H24BrNNa05: 448.07; found: 448.06.
With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 20℃; To a solution of acid MlOb (2.16 g, 9.42 mmol) and 2-bromo-l-(4- bromophenyl)ethanone (2.62 g, 9.42 mmol) in acetonitrile (50 mL) was added slowly diisopropylethylamine (1.645 mL, 9.42 mmol), and the reaction mixture was stirred at room temperature for 5 hr. Solvent was removed in vacuo, and the residue was partitioned between ethyl acetate and water (1 :1, 100 mL). The organic layer was washed with sat. NaHCO3, dried (Na2SO4) and concentrated in vacuo to afford ketoester MlOc as white solid (3.9g), which was used in the next step without further purification. 1H NMR (400 MHz , DMSO-d6} delta - 2.5 ppm): 7.92 (d, J = 8.3, 2H), 7.78 (d, J = 8.5, 2H), 5.6-5.4 (m, 2H), 4.35 (m, IH), 3.85 (m, IH), 2.25 (m, IH), 2.05 (m, 2H), 1.60 (m, IH), 1.5/1.4 (two overlapping br s>; 9H), 1.18 (d, J - 6.6, 3H). LC/MS: Anal. Calcd. for [M+Naf Cj9H2481BrNaNO5: 450.07; found: 450.00.

 

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