10165-86-3|Methyl 6-formylnicotinate| Ambeed

Structure of 10165-86-3

*Storage: {[sel_prStorage]}

*Shipping: {[sel_prShipping]}

4.5 *For Research Use Only !

{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]} Purity: {[proInfo.pro_purity]}

Change View

Size	Price	VIP Price	US Stock	Global Stock	In Stock
{[ item.pr_size ]}		Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}

US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days

{[ item.pr_size ]}

In Stock

- +

Please Login or Create an Account to: See VIP prices and availability

US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks

Quality Control of [ 10165-86-3 ] Purity: 97% SDS Specification

COA

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

NMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

CNMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

HPLC

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

LC-MS

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

1-2 Day Shipping
High Quality
Technical Support

Product Details of [ 10165-86-3 ]

CAS No. :	10165-86-3
Formula :	C₈H₇NO₃
M.W :	165.15
SMILES Code :	C(=O)C1=NC=C(C(=O)OC)C=C1
MDL No. :	MFCD08275010
InChI Key :	BZOWIADSJYMJJJ-UHFFFAOYSA-N
Pubchem ID :	586269

Safety of [ 10165-86-3 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Computational Chemistry of [ 10165-86-3 ] Show Less

Physicochemical Properties

Num. heavy atoms	12
Num. arom. heavy atoms	6
Fraction Csp3	0.12
Num. rotatable bonds	3
Num. H-bond acceptors	4.0
Num. H-bond donors	0.0
Molar Refractivity	40.9
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	56.26 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.11
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	0.5
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	0.68
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	-0.28
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	1.35
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	0.67

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-1.35
Solubility	7.36 mg/ml ; 0.0446 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-1.25
Solubility	9.25 mg/ml ; 0.056 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-2.04
Solubility	1.5 mg/ml ; 0.0091 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	Yes
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	No
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-6.95 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	1.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	1.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	1.44

Application In Synthesis of [ 10165-86-3 ]

* 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 [ 10165-86-3 ]

[ 10165-86-3 ] Synthesis Path-Downstream 1~35

1
[ 872-85-5 ]
[ 109-97-7 ]
[ 10165-86-3 ]
6-((5E,10Z,14Z,19Z)-10,15,20-Tri-pyridin-4-yl-porphyrin-5-yl)-nicotinic acid methyl ester [ No CAS ]

References: [1]Bulletin de la Societe Chimique de France,1996,vol. 133,p. 679 - 689.

2
[ 5470-70-2 ]
[ 10165-86-3 ]

Yield	Reaction Conditions	Operation in experiment
70%	With iodine; trifluoroacetic acid; In dimethyl sulfoxide; at 160℃; for 2h;	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%		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 3.5h;	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.
	With iodine; dimethyl sulfoxide; at 160℃; for 0.25h;	6-Methyl-nicotinic acid methyl ester (5.00 g, 33.1 mmol) was mixed with iodine (8.40 g, 33.1 mmol) and a small amount of DMSO was added to promote mixing. After addition of DMSO (5ml), this solution of added to a heated solution of DMSO (15 ml) at 130°C. The temperature of the mixture is then slowly raised to 160°C and stirred at this temperature for 15 minutes. After cooling down the solution, a small amount of a saturated aqueous solution of Na2CO3 is added. Extraction of the product with diethyl ether. Crude compound used without further purification. 1H NMR (400 MHz, CDCl3, 298K) delta 10.00 (s, 1H, CHO), 9.22 (d, 3J (H, H) = 1.5 Hz, 1 H, ArH), 8.34 (dd, 3J (H, H) = 6.0 Hz ; 2.0 Hz, 1 H, ArH), 7.90 (d, 3J (H, H) = 8.0 Hz, 1 H, ArH), 3.87 (s, 3 H, CH3).

References: [1]Patent: WO2015/69110,2015,A1 .Location in patent: Page/Page column 34; 35.
[2]European Journal of Organic Chemistry,2008,p. 4412 - 4415.
[3]European Journal of Organic Chemistry,2009,p. 4273 - 4283.
[4]Journal of Organic Chemistry,2012,vol. 77,p. 8968 - 8979,12.
[5]Bulletin de la Societe Chimique de France,1996,vol. 133,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,p. 4413 - 4425.
[8]Patent: EP3333157,2018,A1 .Location in patent: Paragraph 0103; 0104.
[9]Chemistry - A European Journal,2007,vol. 13,p. 9277 - 9285.
[10]Patent: CN105524053,2016,A .Location in patent: Paragraph 0361; 0362.
[11]European Journal of Organic Chemistry,2007,p. 4721 - 4730.
[12]Journal of Materials Chemistry,2008,vol. 18,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 .

4
[ 110-91-8 ]
[ 10165-86-3 ]
[ 201852-49-5 ]
6-((E)-1-Morpholin-4-yl-3-phenyl-allyl)-nicotinic acid methyl ester [ No CAS ]

References: [1]Tetrahedron Letters,2000,vol. 41,p. 1303 - 1305.

5
[ 10165-86-3 ]
(1E,2Z)-2-hydrazono-2-phenylacetaldehyde oxime [ No CAS ]
[ 913188-65-5 ]

References: [1]Tetrahedron Letters,2006,vol. 47,p. 7025 - 7029.

6
[ 10165-86-3 ]
4-methyl-α-oximinoacetophenone hydrazone [ No CAS ]
[ 913188-66-6 ]

References: [1]Tetrahedron Letters,2006,vol. 47,p. 7025 - 7029.

7
[ 10165-86-3 ]
hydrazono-(4-methoxy-phenyl)-acetaldehyde oxime [ No CAS ]
[ 913188-67-7 ]

References: [1]Tetrahedron Letters,2006,vol. 47,p. 7025 - 7029.

8
[ 56026-36-9 ]
[ 10165-86-3 ]

Yield	Reaction Conditions	Operation in experiment
97%	With manganese(IV) oxide; In dichloromethane; at 20℃; for 4h;	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 , 97%).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 4h;	(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, 97%). 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, 86%).

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, 85.6%
71.4%		To a solution of oxalyl chloride (2.0 M in dichloromethane, 8.97 mL) in dichloromethane (35 mL) at -78 C was added (methylsulfinyl)methane (2.55 mL, 35.9 mmol) dropwise. This mixture was allowed to stir at -78 C for 10 minutes then methyl 6-(hydroxymethyl)nicotinate (2.0 g, 11.96 mmol, Combi-Blocks) was added. The mixture was allowed to stir for an additional 15 minutes and triethylamine (6.67 mL, 47.9 mmol) was added, and the mixture was stirred for an additional 15 minutes at -78 C. The dry ice-acetone bath was then replaced with an ice-water bath, and the mixture was allowed to stir for 20 minutes. The mixture was quenched with saturated, aqueous NaHC( (15 mL) and the layers were separated. The aqueous layer was extracted with dichlorome thane (3 x 10 mL), and the combined organic fractions were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified via column chromatography (Si(, 50% ethyl acetate/heptanes) to give the title compound (1.41 g, 8.54 mmol, 71.4% yield). MS (ESI+) m/z 166 (M+H)+.
	With Dess-Martin periodane; In dichloromethane; for 3h;	Dess-Martin reagent (207 mg, 0.49 mmol) was added to a stirring solution of 6- hydroxymethyl-nicotinic acid methyl ester (55 mg, 0.33 mmol) in DCM (17 mL). After stirring for 3 h the solvent was removed in vacuo. The residue was purified by flash chromatography on silica gel (elution with n-hexane/EA 4:1) to give the title compound.GCMS (m/z): 165.2
	With manganese(IV) oxide; In dichloromethane; at 20℃; for 4h;	A mixture of methyl 6-( ydroxymethyi)nicotinate (7 g, 37 mmol) and Mn02 (32,3 g,372 mmoi) in DCM ( 200 mL ) was stirred at 20 Q 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/i) to afford methyl 6-formylnicotinate. MS-ESI (m/z): 166.2 (M+i) + (LC-.MSmethod D; Ret. time: 0.36 mm).
	With manganese(IV) oxide; In dichloromethane; at 20℃;	Intermediate 11-14 Step 1 : methyl 6-formylnicotinate To a solution of methyl 6-(hydroxymethyl)nicotinate (30 g, 179.6 mmol) in DCM (500 mL) was added MnC>2 (93.8 g, 1077.8 mmol). The mixture was stirred at room temperture overnight. The reaction mixture was filtered and concentrated. The residue was purified by column chromatography on silica gel eluted with PE/EA = 10/1 to give methyl 6-formylnicotinate. XH NMR (400 MHz, CDC13) delta ppm 3.98 (d, J= 0.78 Hz, 3 H), 8.01 (d, J= 8.0 Hz, 1 H), 8.40 - 8.49 (m, 1 H), 9.29 - 9.38 (m, 1 H), 10.11 (s, 1 H).

References: [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,p. 102 - 121.
[4]Patent: CN104418811,2017,B .Location in patent: Paragraph 0234-0236.
[5]Patent: WO2019/90076,2019,A1 .Location in patent: Page/Page column 541-542.
[6]Advanced Synthesis and Catalysis,2019,vol. 361,p. 2262 - 2267.
[7]Tetrahedron Letters,2006,vol. 47,p. 7025 - 7029.
[8]Tetrahedron,2008,vol. 64,p. 8963 - 8973.
[9]Patent: WO2009/36996,2009,A2 .Location in patent: Page/Page column 86.
[10]Patent: WO2016/106628,2016,A1 .Location in patent: Page/Page column 70.
[11]Patent: WO2016/109221,2016,A1 .Location in patent: Page/Page column 68.
[12]Russian Journal of Organic Chemistry,2017,vol. 53,p. 963 - 970.
Zh. Org. Khim.,2017,vol. 53,p. 951 - 958,8.

9
[ 10165-86-3 ]
[ 107-21-1 ]
[ 849662-01-7 ]

Yield	Reaction Conditions	Operation in experiment
81%	toluene-4-sulfonic acid; In toluene; for 7.5h;Heating / reflux;	6-Formyl-nicotinic acid methyl ester (300 mg, 1.82 mmol) was dissolved in toluene (25 ml) and ethylene glycol (0.33 ml, 5.92 mmol) and p-toluenesulfonic acid (cat) were added. The mixture is refluxed with a dean-stark for 7.5 hours. The solvents are evaporated and the crude product was purified by column chromatography (SiO2, CH2Cl2/MeOH =99/1). The protected aldehyde was obtained as a white solid (310 mg, 81 percent). 1H NMR (400 MHz, CDCl3, 298K) delta 9.18 (d, 3J(H, H) = 1.8 Hz, 1H, ArH), 8.31 (dd, 3J(H, H) = 8.2Hz ; 2.2 Hz, 1H, ArH), 7.59 (d, 3J(H, H) = 8.0 Hz, 1H, ArH), 5.87 (s, 1H, CH), 4.16-4.05 (m, 4 H, CH2), 3.93 (s, 3 H, CH2). 13C NMR (100 MHz, CDCI3, 298K) delta 165.5 (C=O), 161.0 (ArC), 150.5 (ArCH), 138.0 (ArCH), 126.2 (ArC), 120.3 (ArCH), 103.1 (CH), 65.7 (CH2), 52.5 (CH3).

References: [1]Patent: WO2005/33119,2005,A1 .Location in patent: Page/Page column 75; 76.
[2]European Journal of Organic Chemistry,2007,p. 4721 - 4730.

10
[ 1001200-43-6 ]
[ 10165-86-3 ]

References: [1]Tetrahedron,2008,vol. 64,p. 688 - 695.

11
[ 10165-86-3 ]
[ 101-77-9 ]
[ 849662-06-2 ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol; for 3h;	6-Formyl-nicotinic acid methyl ester (30 mg, 0. 18 mmol) and 4,4'-methylene dianiline (17 mg, 0.086 mmol) were dissolved in ethanol (10 ml) and the mixture was stirred for 3 hours. The ligand was obtained by filtration as a white-yellow solid (33 mg, percent). FAB-MS Calcd for C29H24N4O4 m/z= 492.2, Found m/z =493. 1 [M=H]. 1H NMR (400 MHz, CDCl3, 298K) delta 9.28 (d, 1H, 3J(H, H) = 1.5 Hz ArH), 8.67 (s, 1H, CH), 8.39 (d, 3J(H, H) = 8.3 Hz; 2.0 Hz, 1 H, ArH), 8.28 (d, 3J(H, H) = 7.8 Hz, 1 H, ArH), 7.30-7.22 (m, 4H, ArH), 4.05 (s, 1H, CH2), 3.98 (s, 3H, CH3).

References: [1]Patent: WO2005/33119,2005,A1 .Location in patent: Page/Page column 78.

12
[ 110-89-4 ]
[ 10165-86-3 ]
[ 733783-33-0 ]

Yield	Reaction Conditions	Operation in experiment
74%	With sodium tris(acetoxy)borohydride; In dichloromethane; for 18h;	To a solution of <strong>[10165-86-3]6-formyl-nicotinic acid methyl ester</strong> (0.200 g, 1.21 mmol) and piperidine (0.14 mL, 1.33 mmol) in DCM (15 mL) was added NaB(OAc)3H (0.380 g, 1.80 mmol). After 18 h, the reaction was diluted with 1 N NaOH (10 mL) and extracted with DCM (2*50 mL). The organic layers were combined, dried (Na2SO4), and concentrated. Chromatography of the residue (SiO2; 1-3percent 2 M NH3 in MeOH/DCM) gave the title compound as an oil (0.210 g, 74percent).

References: [1]Patent: US2005/222151,2005,A1 .Location in patent: Page/Page column 13.
[2]European Journal of Medicinal Chemistry,2009,vol. 44,p. 4413 - 4425.

13
[ 7664-93-9 ]
[ 10165-86-3 ]
methyl 6-dimethoxymethylnicotinate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With trimethyl orthoformate; In methanol;	PREPARATION 22 Methyl 2-(Dimethoxymethyl)pyridine-5-carboxylate To a solution of <strong>[10165-86-3]methyl 2-formylpyridine-5-carboxylate</strong> (2.00 g, 12.1 mmol) in methanol (20 ml) and trimethyl orthoformate (5 ml) was added H2 SO4 (conc., 1.5 ml). After refluxing overnight, the reaction was cooled and concentrated to a thick slurry and then poured into saturated NaHCO3 (50 ml). The latter was extracted with ether (3*30 ml) and the combined organic layers dried (MgSO4) and concentrated to afford title product (1.91 g, 75percent).

References: [1]Patent: US5061717,1991,A .

14
[ 10165-86-3 ]
[ 149-73-5 ]
methyl 6-dimethoxymethylnicotinate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98.8%		Formic acid (40ml) was slowly added dropwise to a solution of Example 7A (20g, 120mmol) in trimethyl orthoformate(400ml) at 0°C and stirred at this temperature for 30 minutes before concentrated sulfuric acid (1.2ml) wasadded dropwise. After the addition, the reaction solution was heated to 50°C and stirred for 30 minutes and then cooledto 25°C and stirred for another 3 hours. The mixture was cooled to room temperature and added to water (100ml). Theaqueous layer was extracted with ethyl acetate (200ml 3 3). The organic phases were combined, washed with saturatedbrine (100ml 3 2), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to give the title compoundas a brown oil (25g, yield 98.8percent) which was used directly in the next step.

References: [1]Patent: EP3333157,2018,A1 .Location in patent: Paragraph 0105; 0106.
[2]Chemistry - A European Journal,2007,vol. 13,p. 9277 - 9285.
[3]Journal of Materials Chemistry,2008,vol. 18,p. 489 - 494.

15
C₈H₉N₃O [ No CAS ]
[ 10165-86-3 ]
C₁₆H₁₄N₄O₃ [ No CAS ]