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Product Details of [ 186593-31-7 ]

CAS No. :186593-31-7
Formula : C14H19BrN2O3
M.W : 343.22
SMILES Code : O=C(N1[C@H](COC2=CC(Br)=CN=C2)CC1)OC(C)(C)C
MDL No. :MFCD27991477

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Application In Synthesis of [ 186593-31-7 ]

* 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 [ 186593-31-7 ]

[ 186593-31-7 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 74115-13-2 ]
  • [ 161511-85-9 ]
  • [ 186593-31-7 ]
YieldReaction ConditionsOperation in experiment
85% With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; at 20℃; for 48h; To a stirred solution of 1-tert-butoxycarbonyl-2 (5)-AZETIDINE (800 mg, 4.3 mmol) and 3-bromo-5- hydroxypyridine (800 mg, 4.6 mmol), and PPh3 (1.69 g, 6.45 mmol) in THF (50 mL) was slowly added DEAD (1.02 mL, 6.45 mmol). The reaction mixture was stirred at room temperature for 48 h, and concentrated in vacuo. The residue was purified by chromatography with hexane-EtOAc (4: 1) to give a light yellow oil (1.25 g, 85%). H NMR (CDC13) 6 8.29 (d, 1H, J= 2.1 Hz), 8. 28 (d, 1H, J= 2.7 Hz), 7.43 (t, 1H, J= 2.4 Hz), 4.51 (M, 1H), 4.34 (M, 1H), 4. 13 (dd, 1H, J= 10.2, 3.0 Hz), 3. 89 (t, 2H, J= 7.5 Hz), 2.42-2. 22 (M, 2H), 1.43 (s, 9H) ; 13C NMR (CDC13) 8 156.05, 155.35, 143.07, 136.58, 123.96, 120.25, 79.75, 68. 90,59. 84, 47.02, 28. 31,18. 88.
70% With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; A gram-scale synthesis of sazetidine A is outlined in Figure Ia. The Boc-protected azidityl methyl alcohol 2 and 3 -bromo-5 -hydroxy pyridine (3) are both commercially available. Treatment with PPh3 and DEAD according to the Mitsunobu protocol formed ether derivative 4 in 70% yield. Palladium-mediated coupling of the bromo-substituted pyridine 4 with 5-hexyn-l-ol under modified Sonogashira conditions furnished Boc- protected sazetidine A in 73% yield. Deprotection of the Boc-group with HCl was expected to give sazetidine A in salt form as published in the literature. However, after several <n="43"/>AtIy Docket No.: GUX-023.25 attempts, it was found that the HCl salt, especially on larger scale, was a white solid that could be obtained in only moderate yield by a tedious filtration under an inert atmosphere. Exposure of the material to air immediately resulted in decomposition of the material to a yellow-brown wet solid. Therefore, in order to obtain gram quantities of pure sazetidine A, it was found that it was necessary to treat the deprotected material immediately with NH4OH and then isolated the free base of sazetidine A. This product was then taken up in an aqueous solution of HCl to give a solution of the HCl salt of sazetidine A. This modified method gives purer material and was indeed found to be more potent than that reported in the literature.
64% With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; toluene; at 0 - 20℃;Inert atmosphere; Under N2 stream, triphenylphosphine (7.8 g, 29.7 mmol), 40% diethyl azodicarboxylate (40% solution in toluene, 5.2 mL), and 5-bromo-3-hydroxynicotinic acid (5.2 g, 29.7 mmol) at 0 C were added to a solution of 1 (3.6 g, 19.8 mmol) in THF (20 mL). The mixture was stirred at 0 C for 10 min and then warmed to room temperature and stirred overnight. After the reaction, the solvent was removed under reduced pressure followed by silica gel chromatography (petroleum ether/ethylacetate=1/1) to yield 8 (4.35 g, 12.7 mmol, 64%) as a colorless oil. 1HNMR (500 MHz, CDCl3) δ; 8.29 (t, J=2.6 Hz, 2H), 7.45-7.42 (m, 1H),4.55-4.48 (m, 1H), 4.33 (broad s, 1H), 4.13 (dd, J=7.5, 2.9 Hz, 1H),3.89 (m, 2H), 2.39-2.24 (m, 2H), 1.43 (s, 9H). 13C NMR (125 MHz,CDCl3) δ; 156.1, 155.4, 143.2, 136.7, 124.1, 120.3, 79.9, 69.0, 64.2,59.5, 28.4, 19.0. MS (EI+) m/z; 344 ([M+2]+, 1.97), 342 (M+, 1.92),271 (5.59), 269 (5.81), 243 (5.83), 241 (6.09), 156 (28), 113 (22), 100(34), 57 (1 0 0). HRMS (EI+) m/z; 342.0585 (Calcd: 342.0578 forC14H19N2O3Br). [α]D20=-59.63 (c=2.24, CHCl3).
55% With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; toluene; at 10 - 20℃; for 48h;Inert atmosphere; General procedure for Mitsunobu Reaction (Method A). To a mixture of 5-Bromo-3- pyridinol (1.2 equiv) and Ph3P (1.6 equiv) in anhydrous THF taken in a flame-dried flask under N2, N-Boc protected alcohol (1 equiv) was added and the mixture was cooled to - 10 C. Diethyl azodicarboxylate (40% w/v) in toluene (1.6 equiv) was added dropwise to the mixture and was warmed gradually to the room temperature. After 48 h, the reaction mixture was quenched with 1 mL of water and the solvent was removed under reduced pressure. The resulting yellow oil was purified by column chromatography on silica gel to yield 55-60% as a white solid. Example 3(S)-tei"i-butyl-2-((5-bromopyridin-3-yloxy)methyl)azetidine-l-carboxylate (VMY-2-3): Method A was used. Yield 55% (white solid). 1H NMR (400 MHz, CDC13) ? 8.25 - 8.19 (m, 2H), 7.36 (s, 1H), 4.44 (d, J= 5.3, 1H), 4.32 - 4.20 (m, 1H), 4.06 (dd, J = 2.8, 10.1, 1H), 3.81 (t, J= 7.5, 2H), 2.36 - 2.14 (m, 2H), 1.36 (s, 9H). 13C NMR (100 MHz, CDC13 ) ? 156.07,155.41, 143.13, 136.65, 124.02, 120.28, 79.76, 69.00, 59.92,47.14, 28.37, 18.95.HRMS (ESI): exact mass calcd for Ci4Hi9BrN203 [M+H]+, 343.0657, found 343.0670.
With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; 12a. 5-((2S)-Azetidinylmethyloxy)-3-bromopyridine dibenzoate Triphenylphosphine (4.01 g, 15.3 mmol) and DEAD (2.43 mL, 15.3 mnol) were dissolved in 30 mL of THF at 0 C., and the mixture was stirred for 10 minutes. Samples of 1-t-butyloxycarbonyl-2-(S)-azetidinemethanol (2.86 g, 15.3 mmol, Step 7c above) and 3-bromo-5-hydroxypyridine.(1.51 g, 10.2 mmol, Step 10c above) were added, and the mixture was stirred for 40 hours at room temperature. The volatile components were removed under vacuum, and the residue was triturated with hexane. The separated hexane fraction was concentrated, and the residue was chromatographed (silica gel; hexane/ether, 10:1 to 10:2) to afford 5-bromo-3-((1-t-butyloxycarbonyl-(2S)-azetidinyl)methoxy)pyridine as a colorless oil (1.669 g): 1 H NMR (CDCl3, 300 MHz) δ 1.42 (s, 9H), 2.31 (m, 2H), 3.89 (m, 2H), 4.12 (m, 1 H), 4.322 (m, 1 H), 4.52 (m, 1 H), 7.43 (m, 1 H), 8.29 (m, 2H); MS (CI/NH3) m/z 344 (M+H)+.

  • 2
  • [ 161511-85-9 ]
  • [ 458569-33-0 ]
  • [ 186593-31-7 ]
  • 3
  • [ 74115-13-2 ]
  • [ 161511-85-9 ]
  • [ 186593-31-7 ]
YieldReaction ConditionsOperation in experiment
With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; 54b. 5-Bromo-3-(1-BOC-2-(S)-azetidinylmethoxy)pyridine Triphenylphosphine (4.01 g, 15.3 mmol) and DEAD (2.43 mL, 15.3 mmol) were dissolved in 30 mL of THF at 0 C., and the mixture was stirred for for 10 minutes. Samples of 1-BOC-2-(S)-azetidinemethanol (2.86 g, 15.3 mmol), prepared as described above, and 5-bromo-3-hydroxypyridine (1.505 g, 10.2 mmol) were added, and the reaction mixture was stirred for 40 hours at room temperature. The volatiles were removed under vacuum, and the residue was triturated with hexane. The hexane was removed, and the residue was chromatographed on a silica gel column, eluding with hexane:Et2O 10:1 to 10:2 to afford the title compound as a colorless oil (1.669 g). MS (CI/NH3) m/z 344 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ 1.42 (s, 9H), 2.31 (m, 2H), 3.89 (m, 2H), 4.12 (m, 1H), 4.322 (m, 1H), 4.52 (m, 1H), 7.43 (m, 1H), 8.29 (m, 2H).
 

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