CN107216334A - A kind of synthetic method of 6 chlorine furans [3,2 B] pyridine - Google Patents

A kind of synthetic method of 6 chlorine furans [3,2 B] pyridine Download PDF

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Publication number
CN107216334A
CN107216334A CN201710514047.3A CN201710514047A CN107216334A CN 107216334 A CN107216334 A CN 107216334A CN 201710514047 A CN201710514047 A CN 201710514047A CN 107216334 A CN107216334 A CN 107216334A
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China
Prior art keywords
synthetic method
compound
chlorine furans
pyridine
chlorine
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CN201710514047.3A
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Inventor
徐红岩
马敬祥
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Shanghai GL peptide Ltd
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Shanghai GL peptide Ltd
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Priority to CN201710514047.3A priority Critical patent/CN107216334A/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems
    • C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present invention relates to a kind of synthetic method of 6 chlorine furans [3,2 B] pyridine.Mainly solve the technical problem of its synthetic method.Synthetic method of the present invention comprises the following steps：The pyridone of 5 chlorine 3 and iodine, sodium carbonate react at room temperature, generate compound 1；Under the conditions of compound Yuan coupling reactions of 1, and trimethyl acetenyl pasc reaction generation compound 2；Compound 2 and tetrabutyl ammonium fluoride react at room temperature, generate target compound 3.Reaction equation is as follows：

Description

A kind of synthetic method of 6- chlorine furans [3,2-B] pyridine
Technical field
The present invention relates to the synthesis of 6- chlorine furans [3,2-B] pyridine.
Background technology
6- chlorine furans [3,2-B] pyridine（CAS：1142192-61-7）As expensive medicine intermediate, in pharmacy It is used widely in industry.So far, its not disclosed report of related quantization synthetic method.
The content of the invention
It is an object of the invention to provide a kind of synthetic method of 6- chlorine furans [3,2-B] pyridine, its wantage is mainly solved It is combined to the technical problem of method.
Technical solution of the present invention is：A kind of synthetic method of 6- chlorine furans [3,2-B] pyridine, it is characterized in that including following step Suddenly：The first step, 5- chloro-3-hydroxyl pyridines are in water, and the reaction of iodine, sodium carbonate, and reaction solution is acidified with 1 M hydrochloric acid, obtains chemical combination Thing 1；Second step, compound 1 is sub- in bi triphenyl phosphorus palladium chloride and iodate in Isosorbide-5-Nitrae-dioxane and triethylamine mixed liquor Under copper catalysis effect, and trimethyl acetenyl pasc reaction, generate compound 2；3rd step, compound 2 and tetrabutyl ammonium fluoride are anti- Should, furan nucleus is generated, target compound 3 is obtained.
Synthetic line is as follows：
。
First step reaction temperature is room temperature, and the reaction time is 4 hours；Second step reaction temperature is 30-60 DEG C, preferably 45 DEG C, the reaction time is 2-4 hours, preferably 3 hours；Three-step reaction temperature is room temperature, and the reaction time is 1 hour.
The beneficial effects of the invention are as follows：The synthetic line of synthetic method design of the present invention is simple；In whole building-up process, Raw material and reagent are cheap, and intermediate and target product yield are high, it is easy to purify；The blank filled up in its synthetic method.
Embodiment
Embodiment 1：
Step 1：
5- chloro-3-hydroxyl pyridines are added into 250 milliliters of three-necked flasks（5.12 g, 39.7 mmol）, iodine（10.1 g, 39.7 mmol）, sodium carbonate（8.83 g, 83.3 mmol）And water（80 mL）.It is stirred at room temperature after 4 hours, adds 1 M hydrochloric acid（120 mL）, ethyl acetate extraction（50 mL x 3）;Organic phase merges, and uses saturated aqueous common salt（50 mL）Washing, sodium sulphate is dried, mistake Filter.Filtrate is spin-dried for, and crude product is recrystallized in petroleum ether, obtains brown solid, compound 1（9.11 g, 35.8 mmol, 90%）.1H NMR (400 MHz, DMSO-d6): 11.42 (s, 1H), 7.95 (m, 1H), 7.17 (m, 1H) ppm。 LC-MS (ESI): m/z 255.72 [M+H]+；
Step 2：
Compound 1 is added into 100 milliliters of three-necked flasks（1.88 g, 6.27 mmol）, triethylamine（12 mL）With 1,4- dioxies Six rings（12 mL）.Under nitrogen protection, it is separately added into trimethyl acetenyl silicon（1.15 mL, 8.15 mmol）, bi triphenyl Phosphorus palladium chloride（132 mg, 0.188 mmol）And cuprous iodide（71 mg, 0.376 mmol）；3 are stirred during 45 DEG C of reaction solution Hour.Solution is spin-dried for, crude product purified by silica gel pillar layer separation（N-hexane:Ethyl acetate volume ratio=15:1）, obtain orange solid Body, compound 2（1.33 g, 5.89 mmol, 94%）.1H NMR (400 MHz, CDCl3): 8.51 (br s, 1H), 7.79 (s, 1H), 7.14 (s, 1H), 0.38 (s, 9H) ppm。LC-MS (ESI): m/z 226.20 [M+H]+；
Step 3：
Compound 2 is added into 100 milliliters of three-necked flasks（6.0 g, 26.7 mmol)）, dichloromethane（60 mL）With four fourths Base ammonium fluoride（12.8 g, 53.4 mmol）；Stir 1 hour at room temperature.Solution is spin-dried for, crude product purified by silica gel pillar layer separation （Petroleum ether：Ethyl acetate volume ratio=15:1）, obtain white solid, target compound 3（3.48 g, 22.7 mmol, 85%）.1H NMR (400 MHz, DMSO-d6): 8.58 (d, J = 1.6 Hz, 1H), 8.39 (d, J = 2.0 Hz, 1H), 8.36 (s, 1H), 7.21 (d, J = 1.2 Hz, 1H) ppm。LC-MS (ESI): m/z 153.93 [M+H ]+。
Embodiment 2：30 DEG C of second step reaction temperature, the reaction time is 4 hours；Remaining be the same as Example 1.
Embodiment 3：60 DEG C of second step reaction temperature, the reaction time is 2 hours；Remaining be the same as Example 1.

Claims (6)

1. a kind of synthetic method of 6- chlorine furans [3,2-B] pyridine, it is characterized in that comprising the following steps：The first step, the chloro- 3- of 5- Pyridone and iodine, sodium carbonate react at room temperature, reaction solution acidifying, generate compound 1；Second step, Yuan couplings of 1 of compound Under reaction condition, and trimethyl acetenyl pasc reaction, generate compound 2；3rd step, compound 2 and tetrabutyl ammonium fluoride room temperature Lower reaction, generates furan nucleus, obtains target compound 3；Synthetic line is as follows：
。
2. the synthetic method of a kind of 6- chlorine furans [3,2-B] pyridine according to claim 1, it is characterized in that the first step exists Reacted 4 hours in water.
3. the synthetic method of a kind of 6- chlorine furans [3,2-B] pyridine according to claim 1, it is characterized in that the first step is anti- Liquid is answered to be acidified with 1 M hydrochloric acid.
4. the synthetic method of a kind of 6- chlorine furans [3,2-B] pyridine according to claim 1, it is characterized in that second step institute Yuan coupling reaction conditions of Shu are in Isosorbide-5-Nitrae-dioxane and triethylamine mixed liquor, to be reacted at 30-60 DEG C.
5. the synthetic method of a kind of 6- chlorine furans [3,2-B] pyridine according to claim 1, it is characterized in that second step is anti- Answer 2-4 hours.
6. the synthetic method of a kind of 6- chlorine furans [3,2-B] pyridine according to claim 1, it is characterized in that the 3rd step exists Carry out, react 1 hour in dichloromethane.
CN201710514047.3A 2017-06-29 2017-06-29 A kind of synthetic method of 6 chlorine furans [3,2 B] pyridine Withdrawn CN107216334A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114213424A (en) * 2021-12-30 2022-03-22 杭州澳赛诺生物科技有限公司 Synthetic method of furan [3, 2-b ] pyridine derivative

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011138657A1 (en) * 2010-05-04 2011-11-10 Glenmark Pharmaceuticals S.A. Aryl substituted olefinic compounds as pde10a inhibitors
WO2013019653A1 (en) * 2011-07-29 2013-02-07 Tempero Pharmaceuticals, Inc. Compounds and methods
CN103391928A (en) * 2011-03-18 2013-11-13 霍夫曼-拉罗奇有限公司 1,4-oxazepines as bace1 and/or bace2 inhibitors
WO2015165428A1 (en) * 2014-04-30 2015-11-05 Masarykova Univerzita Furopyridines as inhibitors of protein kinases
WO2016010897A1 (en) * 2014-07-14 2016-01-21 Incyte Corporation Bicyclic heteroaromatic carboxamide compounds useful as pim kinase inhibitors
WO2016196244A1 (en) * 2015-05-29 2016-12-08 Incyte Corporation Pyridineamine compounds useful as pim kinase inhibitors

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011138657A1 (en) * 2010-05-04 2011-11-10 Glenmark Pharmaceuticals S.A. Aryl substituted olefinic compounds as pde10a inhibitors
CN103391928A (en) * 2011-03-18 2013-11-13 霍夫曼-拉罗奇有限公司 1,4-oxazepines as bace1 and/or bace2 inhibitors
WO2013019653A1 (en) * 2011-07-29 2013-02-07 Tempero Pharmaceuticals, Inc. Compounds and methods
WO2015165428A1 (en) * 2014-04-30 2015-11-05 Masarykova Univerzita Furopyridines as inhibitors of protein kinases
WO2016010897A1 (en) * 2014-07-14 2016-01-21 Incyte Corporation Bicyclic heteroaromatic carboxamide compounds useful as pim kinase inhibitors
WO2016196244A1 (en) * 2015-05-29 2016-12-08 Incyte Corporation Pyridineamine compounds useful as pim kinase inhibitors

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114213424A (en) * 2021-12-30 2022-03-22 杭州澳赛诺生物科技有限公司 Synthetic method of furan [3, 2-b ] pyridine derivative

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