Methyl 6-aminonicotinate

Methyl 6-aminonicotinate Property

Melting point:

158-162 °C (lit.)

Boiling point:

304.5±22.0 °C(Predicted)

Density 

1.238±0.06 g/cm3(Predicted)

storage temp. 

Keep in dark place,Sealed in dry,Room Temperature

solubility 

DMSO, Methanol

pka

4.78±0.13(Predicted)

form 

Powder

color 

White to light yellow-beige or pink

InChI

InChI=1S/C7H8N2O2/c1-11-7(10)5-2-3-6(8)9-4-5/h2-4H,1H3,(H2,8,9)

InChIKey

JACPDLJUQLKABC-UHFFFAOYSA-N

SMILES

C1=NC(N)=CC=C1C(OC)=O

CAS DataBase Reference

36052-24-1(CAS DataBase Reference)

Safety

Hazard Codes 

Xi,Xn

Risk Statements 

36/37/38-20/21/22

Safety Statements 

26-36-36/37

RIDADR 

2811

WGK Germany 

3

HazardClass 

IRRITANT

HS Code 

29333990

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P271Use only outdoors or in a well-ventilated area.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

Methyl 6-aminonicotinate Chemical Properties,Usage,Production

Chemical Properties

Off-White Solid

Uses

Methyl 6-aminonicotinate can be used in ointments for treatment of psoriasis.

Synthesis

GENERAL STEPS: A mixture of 6-aminonicotinic acid (4.0 g, 28.9 mmol), methanol (75 mL) and concentrated hydrochloric acid (4 mL) was placed in a reflux apparatus and heated to reflux the reaction for 16 hours. Upon completion of the reaction, the mixture was cooled to 25 °C and subsequently concentrated under reduced pressure by rotary evaporator to remove methanol. Water (20 mL) was added to the residual solid and the pH was adjusted with sodium bicarbonate to 8. Subsequently, extraction was performed with ethyl acetate (3 x 25 mL). The organic phases were combined, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give methyl 6-aminonicotinate (3.12 g, 71% yield) as a white foamy solid: EI-HRMS m/e Calculated value of C7H8N2O2 (M+) 152.0586, measured value 152.0586. [0199] 2-(4-Methylsulfonyl-3-trifluoromethyl-phenyl)-3-(tetrahydro-pyran-2-yl)-propionic acid (prepared according to the method of Example 12, 300 mg, 0.79 mmol) was dissolved in dichloromethane (6 mL), N,N-dimethylformamide (7 drops) was added, and then cooled to 0°C. To this solution was added 2.0 M dichloromethane solution of oxalyl chloride (0.48 mL, 0.95 mmol) dropwise. The reaction mixture was stirred at 0 °C for 30 min and then slowly warmed to 25 °C, followed by concentration under reduced pressure to remove the solvent and excess oxalyl chloride. The resulting residue was redissolved in anhydrous tetrahydrofuran (6 mL) and a tetrahydrofuran (5 mL) solution of methyl 6-aminonicotinate (252 mg, 1.67 mmol) and 2,6-dimethylpyridine (0.48 mL, 3.95 mmol) were added dropwise. The reaction mixture was stirred at 25 °C for 16 h before being diluted with water (100 mL) and extracted with dichloromethane (3 x 50 mL). The organic phases were combined, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Purification by Biotage Fast Chromatography System (FLASH 40S, silica gel column, elution gradient 7/3 hexane/ethyl acetate to 1/1 hexane/ethyl acetate) afforded methyl 6-[2-(4-methylsulfonyl-3-trifluoromethyl-phenyl)-3-(tetrahydro-pyran-2-yl)-propanoylamino]-nicotinate (227 mg, 55% yield) as a white Frothy solid: E23-HRMS m/e Calculated value C23H25F3N2O6S(M+H)+ 537.1277, measured value 537.1284.

References

[1] Organic Letters, 2018, vol. 20, # 15, p. 4393 - 4396
[2] European Journal of Medicinal Chemistry, 2017, vol. 140, p. 42 - 51
[3] Patent: WO2015/105779, 2015, A1. Location in patent: Page/Page column 11
[4] Patent: US2016/333005, 2016, A1. Location in patent: Paragraph 0041
[5] Patent: US2015/166535, 2015, A1. Location in patent: Paragraph 0039; 0040