Methyl 1-aminocyclopropanecarboxylate hydrochloride

Methyl 1-aminocyclopropanecarboxylate hydrochloride is White Crystalline Solid

Preparation of methyl 1-aminocyclopropanecarboxylate hydrochloride; Acetyl chloride (10 mL) was added dropwise with stirring to MeOH (10 mL). The resultant solution was added dropwise to a suspension of 1-aminocyclopropanecarboxylic acid, (2.5 g, 24.7 mmol) in MeOH (20 mL) and the reaction refluxed for 16 h. The reaction was cooled and concentrated in-vacuo to give methyl 1-aminocyclopropanecarboxylate hydrochloride (3.77 g, 100percent), MS: m/z=116.2 (calcd. for C5HA solution of 1-aminocyclopropylcarboxylic acid (202 mg, 2 mmol) was dissolved in 10 mL of anhydrous methanol, and 0.3 mL of thionyl chloride was added dropwise to the ice bath. The ice bath was removed and heated to reflux overnight. The solvent was distilled off under reduced pressure, 1-aminocyclopropylcarboxylic acid methyl ester hydrochloride 300mg, the yield of 99percentWhite solid, 1-aminocyclopropanecarboxylic acid (1.46 g, 14.45 mmol) and methanol (50 ml) were charged. An ice bath was set and thionyl chloride (2.6 ml, 36.12 mmol) was slowly added thereto. Then, the ice bath was removed, and the mixture was stirred at room temperature for 4 hours. The resultant product was vacuum-distilled to remove a solvent, and dried in a 60°C oven so as to obtain methyl-1-aminocyclopropanecarboxylate hydrochloride (2.08 g, 13.72 mmol, 98 percent).[637] 1-aminocyclopropanecarboxylic acid (1.46 g, 14.45 mmol) and methanol (50 ml) were charged. a) Preparation of 1-amino-cyclopropane carboxylic acid methylester hydrochloride: 1-Aminocyclopropane-i -carboxylic acid (2 g; 19.78 mmol) is suspended in water free methanol (50 ml) and cooled to 0General procedure: A mixture of 5-(N-(2-chloro-5-(trifluoromethyl) phenyl) sulfamoyl)-4-methylthiophene-2-carboxylic acid (200 mg, 0.50 mmol), (R)-methyl 2-amino-3-phenylpropanoate, HCl (129 mg, 0.60 mmol), DIEA (0.35 ml, 2.0 mmol) in DMF (1 ml) was stirred overnight. The solvent was removed under reduced pressure and the crude material was diluted with ethyl acetate (50 mL). The organic layer was washed with water (25 mL) and dried over sodium sulfate. The mixture was filtered and the solution was concentrated. The crude material was purified by Biotage column chromatography eluting with an ethyl acetate/hexane gradient to afford (R)-methyl 2-(5-(N-(2-chloro-5-(trifluoromethyl) phenyl) sulfamoyl)-4-methylthiophene-2-carboxamido)-3-phenylpropanoate (200 mg, 71%).3.0 g (20.0 mmol, 1.0 eq) of 3.0 g (2.0 mmol, 1.0 eq) of Methyl 1-aminocyclopropanecarboxylate hydrochloride (40 mg, 0.27 mmol) was added to a stirred suspension of 4- [2-(3 -pyridinyl)-2H-indazol-5 -yl] -2-pyridinecarboxylic acid (70 mg, 0.22 mmol) and HATU (100 mg, 0.26 mmol) in DMF (4 mL). The reaction mixture wasstirred at room temperature for 1 hour, DIPEA (115 1iL, 0.66 mmol) was added, and stirring was continued overnight. The reaction mixture was then concentrated under reduced pressure, and the residue was purified by IVIPLC (12 g silica, 0-10percent MeOH in dichloromethane) to obtain the title compound (80 mg) as white solid. 'H NIVIR (500 MHz, DMSO-d6): ppm9.29-9.45 (m, 2H), 8.64-8.77 (m, 2H), 8.49-8.59 (m, 1H), 8.3 1-8.40 (m, 1H), 8.09-8.22 (m, 1H), 7.98-8.07 (m, 1H), 7.88-7.96 (m, 1H), 7.79-7.87 (m, 1H), 7.62- .72 (m, 1H), 3.66 (s, 3H), 1.42-1.54 (m, 2H), 1.23-1.28 (m, 2H).

It is used in pharmaceutical compositions.

Molecular Weight:151.59
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:151.0400063
Monoisotopic Mass:151.0400063
Topological Polar Surface Area:52.3
Heavy Atom Count:9
Complexity:118
Covalently-Bonded Unit Count:2
Compound Is Canonicalized:Yes