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Chemical Structure| 57543-67-6

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Product Details of [ 57543-67-6 ]

CAS No. :57543-67-6
Formula : C10H6ClNO
M.W : 191.61
SMILES Code : N#CC(CO1)=CC2=C1C=CC(Cl)=C2
MDL No. :MFCD00052359
InChI Key :KHQQZPGTELLAOG-UHFFFAOYSA-N
Pubchem ID :1475920

Safety of [ 57543-67-6 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338

Application In Synthesis of [ 57543-67-6 ]

* 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 [ 57543-67-6 ]

[ 57543-67-6 ] Synthesis Path-Upstream   1~1

  • 1
  • [ 57543-67-6 ]
  • [ 83823-06-7 ]
YieldReaction ConditionsOperation in experiment
65%
Stage #1: With sodium hydroxide In tetrahydrofuran; water for 4 h; Heating / reflux
Stage #2: With hydrogenchloride In tetrahydrofuran; water
5-chloro-2-hydroxy-benzaldehyde Compound 15a (10.0 mmol, 1.7 g), acrylonitrile(50.0 mmol, 2.14 mL) and DABCO (2.33 mmol, 0.26 g) were mixed together and heated toreflux overnight using an oil bath. After the flask was cooled to room temperature, Et2O (100mL) was added and the Et2O layer was washed with 10percent NaOH solution followed by IN HCland brine. The organic layer was dried over MgSO4, filtered and the solvent was removed invacuo to obtain 6-chloro-2H-chromene-3-carbonitrile Compound 15b as a yellow solid (1.42 g,74percent), which was used in the next step without further purification (the preceding was describedin Wise, L. et al. J. Med. Chem., 1988, 31, 688).; THF (2 mL) and 10percent NaOH solution (100 mL) was added to a round bottom flaskcontaining Compound 15b (7.43 mmol, 1.42 g). The solution was heated to reflux for 4 hrs.The flask was immersed in an ice-bath and the solution was acidified by careful addition ofcone. HCl. The resulting pale yellow solid was filtered and dried in a vacuum oven to obtain 6-chloro-2H-chromene-3-carboxylic acid Compound 15c (1.02 g, 65percent).; Sodium triacetoxyborohydride (3.5 mmol, 0.75 g) was added to a mixture of 4-nitro-fnmnmitirl tlf\\ O K mmnl fl 47 cA ('9.<\\^-hirl\\/f Inf? 7 nhpnt-9-vlaminp <~.rmnminrl15d (3.0 mmol, 0.33 g) and glacial acetic acid (3 drops) in CH2C12 (40 mL). The resultingsuspension was allowed to stir at room temperature for 12 hrs. An aliquot of the reactionmixture showed the formation of product (MS m/e 247,100percent). An aqueous solution offormaldehyde (37percent solution, 9.6 mmol, 0.8 mL) was added to the reaction mixture followed bysodium triacetoxyborohydride (3.5 mmol, 0.75 g) and the mixture was allowed to stir at r.t. for2 hrs. The reaction mixture was basified with 2N NaOH solution and was extracted withCH2C12. The organic layer was washed with brine, separated and dried over Na2SO4. Thedrying agent was filtered and the solvent was removed in vacua to obtain (25)-bicyclo[2.2,l]hept-2-yl-methyl-(4-nitro-benzyl)-amine Compound 15e (0.72 g, 98percent) as anorange oil. MS m/e 261 (M+H, 100percent), which was used in the next step without furtherpurification.; SnCl2.2H2O (10.4 mmol, 2.35 g) was added to a solution of Compound 15e (2.76mmol, 0.72 g) in EtOH (25 mL) at r.t. The resulting yellow solution was stirred for 2 days.The solvent was removed in vacua and the resulting residue was basified with 2N NaOHsolution and the aqueous layer was extracted with CH2C12 (2 X 30 mL). The combined organiclayers were dried over Na2SC>4, filtered and the solvent was removed in vacuo to obtain (25)-(4-amino-benzyl)-bicyclo[2.2.1]hept-2-yl-methyl-amine Compound 15f (0.54 g, 85percent yield) as athick yellow oil. MS m/e 231 (M+H, 100percent), which was used in the next step without furtherpurification.; EDCI (0.33 mmol, 0.07 g) was added in one portion to a suspension of Compound 15f(0.24 mmol, 0.06 g), 6-ch]oro-2H-chromene-3-carboxylic acid Compound 15g (0.22 mmol,0.04 g) and HO'Bt (0.22 mmol, 0.03 g) in DMF (5,0 mL) at 0°C. The resulting suspension waswarmed to r.t. and then a crystal of DMAP and Et3N (0.65 mmol, 0.1 mL) was added and thereaction mixture was stirred overnight. The orange-yellow suspension was poured in water andwas extracted with EtOAc (25 mL). The organic layer was washed with water (2 X 20 mL)followed by 5percent NaOH solution (10 rnL) and brine. The organic layer was separated, driedover NajSCM and filtered. The solvent was removed iirvacuo and the resulting residue wast ''purified by preparative TLC (15:1 CH2Cl2/MeOH) to yield 6-chloro-2H-chromene-3-carboxylicacid (2>S)-{4-[(bicyclo[2.2.1]hept-2-yl-methyl-amino)-methyl]-phenyl}-amide Compound ISh(0.06 g, 61percent) as a pale yellow solid. MS m/e 423 (M+H, 100percent).; lodomethane (0.5 mL) was added to a solution of Compound 15h (0.08 mmol, 0,03 g)in CH2C12 (1.0 mL) at r.t. and the resulting solution was allowed to stand overnight. A yellowprecipitate was observed and the solvent was removed in vacua. The resulting yellow solidwas washed with Et2O to obtain Compound 110 (0.05 g, 96percent) as a yellow solid. MS m/e 437(M+H, 100percent).
65%
Stage #1: With sodium hydroxide; water In tetrahydrofuran for 4 h; Heating / reflux
Stage #2: With hydrogenchloride; water In tetrahydrofuran
THF (2 mL) and 10percent NaOH solution (100 mL) was added to a round bottom flask containing Compound 15b (7.43 mmol, 1.42 g). The solution was heated to reflux for 4 hrs. The flask was immersed in an ice-bath and the solution was acidified by careful addition of conc. HCl. The resulting pale yellow solid was filtered and dried in a vacuum oven to obtain 6-chloro-2H-chromene-3-carboxylic acid Compound 15c (1.02 g, 65percent).
References: [1] Archiv der Pharmazie, 2012, vol. 345, # 10, p. 767 - 770.
[2] Patent: WO2006/12135, 2006, A1, . Location in patent: Page/Page column 75-77.
[3] Patent: US2006/293379, 2006, A1, . Location in patent: Page/Page column 81.
[4] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1982, vol. 21, # 4, p. 344 - 347.
[5] RSC Advances, 2014, vol. 4, # 102, p. 58397 - 58403.
[6] Bioorganic and Medicinal Chemistry, 2019, vol. 27, # 7, p. 1382 - 1390.
 

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