[ CAS No. 10165-86-3 ]

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CAS No. :10165-86-3MDL No. :MFCD08275010
Formula :C8H7NO3InChI Key :BZOWIADSJYMJJJ-UHFFFAOYSA-N
M.W :165.15Pubchem ID :586269
Boiling Point :272.9°C at 760 mmHg
Synonyms :

Computed Properties

TPSA : 56.3 H-Bond Acceptor Count : 4
XLogP3 : 0.5 H-Bond Donor Count : 0
SP3 : 0.13 Rotatable Bond Count : 3

Safety

Signal Word:WarningClassN/A
Precautionary Statements:P261-P305+P351+P338UN#:N/A
Hazard Statements:H315-H319-H335Packing Group:N/A
GHS Pictogram:

Application In Synthesis

[ 10165-86-3 ] Synthesis Path-Upstream   1~8

  • 1
  • [ 56026-36-9 ]
  • [ 10165-86-3 ]
YieldReaction ConditionsOperation in experiment
97% With manganese(IV) oxide In dichloromethane at 20℃; for 4.00 h; A mixture of methyl 6-(hydroxymethyl)nicotinate (7 g , 37 mmol) and Mn02 (32,3 g , 372 mmol) in DCM ( 200 mL ) was stirred at 20 °C for 4 hours. The mixture was filtered and the filtrate was concentrated. The residue was purified by column chromatography on silica gel (PE/EtOAc = 5/1) to afford methyl 6-formylnicotinate (6 g , 97percent).MS-ESI (m/z): 166.2 (M+l) + (LC-MS method C; Ret. time: 0.36 min).
97% With manganese(IV) oxide In dichloromethane at 20℃; for 4.00 h; (c)
methyl 6-formylnicotinate
A mixture of methyl 6-(hydroxymethyl)nicotinate (7 g, 37 mmol) and MnO2 (32.3 g, 372 mmol) in DCM (200 mL) was stirred at 20° C. for 4 hours.
The mixture was filtered and the filtrate was concentrated.
The residue was purified by column chromatography on silica gel (PE/EtOAc=5/1) to afford methyl 6-formylnicotinate (6 g, 97percent). MS-ESI (m/z): 166.2 (M+1)+ (LC-MS method C; Ret. time: 0.36 min).
86% With Dess-Martin periodane In dichloromethane at 20℃; Inert atmosphere Dess-Martin periodinane (3.0 g, 7.2 mmol) was added slowly to the mixture of compound 38 (1.0 g,6.0 mmol) in DCM (10 mL). The resulting mixture continued to stir at room temperature overnight.The reaction was quenched with water. The aqueous phase was extracted with EtOAc. The combinedorganic phases were then processed in the usual way and chromatographed (3:1 petroleum ether/EtOAc)to yield compound 39 (0.85 g, 86percent).
85.6% With Dess-Martin periodane In dichloromethane The A solution of compound 25 (1.0 g, 6. Ommol)Dissolved in dichloromethane (10 mL)in,Add a Dess-Martin periodinane(3.0 g, 7.2 mmo 1)TLC to track the degree of completion of the assay,After the reaction is completed,Water extraction, ethyl acetate extraction,Concentration gave compound 26 (0.6 g, 85.6percent

Reference: [1] Patent: WO2014/114185, 2014, A1. Location in patent: Page/Page column 126
[2] Patent: US2014/206681, 2014, A1. Location in patent: Paragraph 0782
[3] Molecules, 2014, vol. 19, # 1, p. 102 - 121
[4] Patent: CN104418811, 2017, B. Location in patent: Paragraph 0234-0236
[5] Tetrahedron Letters, 2006, vol. 47, # 39, p. 7025 - 7029
[6] Tetrahedron, 2008, vol. 64, # 37, p. 8963 - 8973
[7] Patent: WO2009/36996, 2009, A2. Location in patent: Page/Page column 86
[8] Patent: WO2016/106628, 2016, A1. Location in patent: Page/Page column 70
[9] Patent: WO2016/109221, 2016, A1. Location in patent: Page/Page column 68
[10] Russian Journal of Organic Chemistry, 2017, vol. 53, # 7, p. 963 - 970[11] Zh. Org. Khim., 2017, vol. 53, # 7, p. 951 - 958,8
  • 2
  • [ 5470-70-2 ]
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YieldReaction ConditionsOperation in experiment
70% With iodine; trifluoroacetic acid In dimethyl sulfoxide at 160℃; for 2.00 h; A mixture of methyl 6-methylnicotinate (5.0 g, 33.0 mmol), 12 (8.4 g, 33.2 mmol) andTFA (7.5 mL, 11.5 g, 0.1 mol) in DMSO (100 mL) was heated to 160°C for 2 h. Themixture was allowed to cool to RT and poured into a 1 N solution ofNa2S2O3 (aq.) (0.5L) solution, made alkaline using NaOH (2 N) and extracted with EtOAc (3 x 0.2 L).The combined organic layers were dried (Na2SO4) and concentrated in vacuo. The residue was dissolved in DCM and applied on a short pad of silica. The product was eluted with EtOAc to afford the product as a yellowish solid (3.8 g, 23 mmol, 70percent).
46%
Stage #1: With iodine; tert-Butyl iodide; trifluoroacetic acid In dimethyl sulfoxide at 160℃; for 3.00 h;
Stage #2: With sodium thiosulfate In water; dimethyl sulfoxide
Stage #3: With sodium hydrogencarbonate In water; dimethyl sulfoxide
A solution of 6-methyl nicotinic acid methyl ester (1.00 g, 6.62 mmol), iodine (1.68 g, 6.62 mmol), 2-iodo-2-methylpropane (0.478.g, 2.60 mmol) and trifluoroacetic acid (2.26 g, 19.8 mmol) in anhydrous DMSO was heated for 3 h at 160° C.
The reaction mixture was cooled to room temperature (rt) and treated with 1 N aq. Na2S2O3 (50 mL).
The reaction mixture was adjusted to pH 10 with 1 N aq. NaHCO3.
The reaction mixture was extracted with ethyl acetate (3*100 mL).
The combined organic phases were dried over anhydrous Na2SO4, filtered, and concentrated.
Chromatography of the residue (SiO2; 0-3percent EtOH:DCM) gave the title compound as a solid (0.506 g, 46percent).
37% With iodine; trifluoroacetic acid In dimethyl sulfoxide at 0 - 140℃; for 3.50 h; Iodine (33.5g, 0.13mmol) and trifluoroacetic acid (35.3ml, 0.4mmol) were added to a solution of methyl 6-carboxylate-1-picoline (20g, 0.13mol) in N,N-dimethylsulfoxide (200ml) at 0°C and the mixture was stirred for 1 hourand then heated to 140°C and stirred for 2.5 hours. After being cooled to 0°C, the reaction was quenched with saturatedsodium thiosulfate solution (30ml) and stirred for 30 minutes. The aqueous layer was extracted with ethyl acetate (150ml3 3) and the organic layers were combined and washed with brine (50ml 3 2), dried over anhydrous sodium sulfate,filtered, concentrated in vacuo and the residue was purified by flash silica gel column chromatography to give the titlecompound (8g, yield 37percent). 1H NMR (400MHz, CHLOROFORM-d) ppm :10.14 (s, 1H), 9.36 (s, 1H), 8.47 (dd, J=1.3, 8.0Hz, 1H), 8.03 (d, J=8.0 Hz, 1H), 4.05 - 3.94 (s, 3H).
15% With selenium(IV) oxide In 1,4-dioxane at 85℃; Inert atmosphere 250mL single-neck flask was added methyl 6-methylpyridine-3-carboxylate (10g, 66.15mmol) and 1,4-dioxane (100mL), was added under stirring selenium dioxide (14.7g, 132mmol), nitrogen heated to 85 under the protection of the reaction overnight. Cooling to room temperature, filtered, and the solvent was removed by rotary evaporation, the crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 1/1), give a pale yellow solid 1.6g, Yield: 15percent.

Reference: [1] Patent: WO2015/69110, 2015, A1. Location in patent: Page/Page column 34; 35
[2] European Journal of Organic Chemistry, 2008, # 26, p. 4412 - 4415
[3] European Journal of Organic Chemistry, 2009, # 25, p. 4273 - 4283
[4] Journal of Organic Chemistry, 2012, vol. 77, # 20, p. 8968 - 8979,12
[5] Bulletin de la Societe Chimique de France, 1996, vol. 133, # 7-8, p. 679 - 689
[6] Patent: US2005/222151, 2005, A1. Location in patent: Page/Page column 12-13
[7] European Journal of Medicinal Chemistry, 2009, vol. 44, # 11, p. 4413 - 4425
[8] Patent: EP3333157, 2018, A1. Location in patent: Paragraph 0103; 0104
[9] Chemistry - A European Journal, 2007, vol. 13, # 33, p. 9277 - 9285
[10] Patent: CN105524053, 2016, A. Location in patent: Paragraph 0361; 0362
[11] European Journal of Organic Chemistry, 2007, # 28, p. 4721 - 4730
[12] Journal of Materials Chemistry, 2008, vol. 18, # 4, p. 489 - 494
[13] Patent: WO2005/33119, 2005, A1. Location in patent: Page/Page column 75-76
[14] Patent: WO2014/114185, 2014, A1
[15] Patent: US2014/206681, 2014, A1
[16] Patent: WO2016/106628, 2016, A1
  • 3
  • [ 17874-79-2 ]
  • [ 10165-86-3 ]
YieldReaction ConditionsOperation in experiment
62% With Dess-Martin periodane In dichloromethane at 0℃; for 6.00 h; 10314] Dimethyl-2,5-pyridinedicarboxylate (960 mg, 4.9mmoles) and CaC12 (2.198 g, 19.7 mmoles) were added to a dried flask. THF (11 mE) and EtOH (12 mE) were added, and the resulting suspension was stirred on ice for 30 minutes. NaI3H4 (465 mg, 12.3 mmoles) was added portion wise with stirring. The reaction was allowed to come to room temperature overnight. Afier 18 h, the reaction was quenched by the dropwise addition of an aqueous solution of NH4C1 (saturated aqueous NH4C1 [20 mE] plus H20 [40 mE]) while stirring on ice. The aqueous layer was extracted with DCM (4x30 mE) and the combined organics were dried over Na2SO4(s) and concentrated under reduced pressure to afford the crude alcohol (678 mg) as a pale yellow solid. The crude alcohol was dissolved in dry DCM (45 mE), after which Dess-Martin periodinane (2.6 g, 6.1 mmoles) was added portion wise while stirring on ice. After 6 h, the reaction was quenched by the dropwise addition of a solution of 5percent Na2S2O3 in half saturated NaHCO3 (80 mE). The aqueous layer was extracted with DCM (3x40 mE). The combined organics were dried over Na2SO4(s) and concentrated under reduced pressure to afford the title compound (504 mg, 62percent) as a pale yellow solid. ‘H NMR (400 MHz, CDC13) ö 10.16 (s, 1H), 9.38 (dd, J=0.5, 2.0 Hz, 1H), 8.49 (dd, J=2.0, 8.0 Hz, 1H), 8.05 (dd, J=0.5, 8.0 Hz, 1H), 4.02 (s, 1H); ‘3C NMR (100 MHz, CDC13) ö 192.6, 164.8, 154.9, 151.2, 138.3, 121.1, 52.9; HRMS (El) mlz 165.0415 [calc’d for C8H7N03 (M) 165.042 1]
Reference: [1] Patent: US2016/280701, 2016, A1. Location in patent: Paragraph 0312; 0313; 0314
  • 4
  • [ 932382-16-6 ]
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Reference: [1] Organic Letters, 2014, vol. 16, # 2, p. 390 - 393
  • 5
  • [ 881-86-7 ]
  • [ 10165-86-3 ]
Reference: [1] Molecules, 2014, vol. 19, # 1, p. 102 - 121
[2] Patent: WO2016/106628, 2016, A1
[3] Patent: US2016/280701, 2016, A1
[4] Patent: CN104418811, 2017, B
[5] Russian Journal of Organic Chemistry, 2017, vol. 53, # 7, p. 963 - 970[6] Zh. Org. Khim., 2017, vol. 53, # 7, p. 951 - 958,8
  • 6
  • [ 1001200-43-6 ]
  • [ 10165-86-3 ]
Reference: [1] Tetrahedron, 2008, vol. 64, # 4, p. 688 - 695
  • 7
  • [ 100-26-5 ]
  • [ 10165-86-3 ]
Reference: [1] Molecules, 2014, vol. 19, # 1, p. 102 - 121
[2] Patent: US2016/280701, 2016, A1
[3] Patent: CN104418811, 2017, B
  • 8
  • [ 49668-89-5 ]
  • [ 10165-86-3 ]
Reference: [1] Patent: WO2014/114185, 2014, A1
[2] Patent: US2014/206681, 2014, A1
[3] Patent: WO2016/106628, 2016, A1
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