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Product Details of 2-Bromo-3-pyridinamine

CAS No. :39856-58-1
Formula : C5H5BrN2
M.W : 173.01
SMILES Code : NC1=CC=CN=C1Br
MDL No. :MFCD00234064
InChI Key :HKDVVTLISGIPFE-UHFFFAOYSA-N
Pubchem ID :642816

Safety of 2-Bromo-3-pyridinamine

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P301+P312-P302+P352-P304+P340-P305+P351+P338

Application In Synthesis of 2-Bromo-3-pyridinamine

* 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.

  • Upstream synthesis route of [ 39856-58-1 ]
  • Downstream synthetic route of [ 39856-58-1 ]

[ 39856-58-1 ] Synthesis Path-Upstream   1~4

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  • [ 42242-11-5 ]
References: [1] Journal of the Chemical Society, 1952, p. 2042,2044.
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  • [ 24424-99-5 ]
  • [ 116026-98-3 ]
YieldReaction ConditionsOperation in experiment
62%
Stage #1: With lithium hexamethyldisilazane In tetrahydrofuran at 0℃; for 0.5 h;
Stage #2: at 20℃; for 1.5 h;
Step 1 : fert-Butyl 2-bromopyridin-3-ylcarbamate (10a)To a solution of 2-bromopyridin-3-amine (3.0 g, 17.3 mmol) in THF (30 mL) was added lithium bis(trimethylsilyl)amide (1 M, 35 mL, 35 mmol) slowly at 0°C and the mixture was stirred at this temperature for 30 min. (Boc)20 (3.9 g, 17.3 mmol) in THF (20 mL) was added and the mixture was stirred at rt for 1.5 h. The reaction mixture was poured into 0.1 M of HCI and extracted with EA. The combined organic layers were extracted with brine, dried and concentrated under reduced pressure. The crude product was purified by CC (PE/EA = 5/1) to give compound 10a (2.9 g, 62percent) as a white solid.
50.7%
Stage #1: With dmap In tetrahydrofuran for 3 h; Reflux
Stage #2: With potassium carbonate In tetrahydrofuran; methanol at 20℃; for 3 h; Reflux
Example 120A
tert-butyl 2-bromopyridin-3-ylcarbamate
To a solution of 2-bromopyridin-3-amine (5.0 g, 28.9 mmol) in THF (50 mL) was added Boc2O (18.92 g, 87 mmol) and DMAP (0.353 g, 2.89 mmol).
The resulting mixture was refluxed for about 3 hours, cooled to room temperature and K2CO3 (11.98 g, 87 mmol) and 50 mL of MeOH were added respectively.
The resulting mixture was stirred at reflux for about 3 hours, then cooled to room temperature, filtrated, and concentrated to give the crude product.
The residue was chromatographed on silica gel column (50:1 Hexanes/EtOAc) to afford the product as a white solid (4.0 g, yield: 50.7percent).
1H NMR (400 MHz, CDCl3): δ 8.45-8.47 (d, 1H, J=8 Hz), 7.02-8.03 (d, 1H, J=4.4 Hz), 7.23-7.26 (m, 1H), 7.05 (s, 1H), 1.55 (s, 9H).
50.7%
Stage #1: With dmap In tetrahydrofuran for 3 h; Reflux
Stage #2: With methanol; potassium carbonate In tetrahydrofuran for 3 h; Reflux
tert-butyl 2-bromopyridin-3-ylcarbamate[204] To a solution of 2-bromopyridin-3-amine (5.0 g, 28.9 mmol) in THF (50 mL) was added Boc20 (18.92 g, 87 mmol) and DMAP (0.353 g, 2.89 mmol). The resulting mixture was refluxed for about 3 hours, cooled to room temperature and K2CO3 (1 1.98 g, 87 mmol) and 50 mL of MeOH were added respectively. The resulting mixture was stirred at reflux for about 3 hours, then cooled to room temperature, filtrated, and concentrated to give the crude product. The residue was chromatographed on silica gel column (50: 1 Hexanes/EtOAc) to afford the product as a white solid (4.0 g, yield: 50.7 percent). *H NMR (400 MHz, CDCI3): ? 8.45-8.47 (d, IH, J= 8 Hz), 7.02-8.03 (d, IH, J= 4.4 Hz), 7.23-7.26 (m, IH), 7.05 (s, IH), 1.55 (s, 9H).
References: [1] Journal of Medicinal Chemistry, 2009, vol. 52, # 16, p. 5032 - 5043.
[2] Patent: WO2013/64231, 2013, A1, . Location in patent: Page/Page column 51.
[3] Patent: US2013/131036, 2013, A1, . Location in patent: Paragraph 1676; 1677.
[4] Patent: WO2013/62966, 2013, A2, . Location in patent: Paragraph 203; 204.
[5] Patent: WO2005/21529, 2005, A1, . Location in patent: Page/Page column 31.
[6] Patent: WO2019/16269, 2019, A1, . Location in patent: Page/Page column 84.
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  • [ 39856-58-1 ]
  • [ 1538-75-6 ]
  • [ 116026-98-3 ]
References: [1] Patent: WO2009/140642, 2009, A2, . Location in patent: Page/Page column 85.
  • 4
  • [ 39856-58-1 ]
  • [ 24424-99-5 ]
  • [ 7440-44-0 ]
  • [ 116026-98-3 ]
References: [1] Patent: US6281227, 2001, B1, .
 

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