Hydrochloric Acid → HCID 59736112, compound

A mixture of 2,2-Dimethyl-thiomorpholine-3-carboxylic acid (3.51 g, 20 mmol, BE 893025), formic acid (5.12 g of 90%) and formalin (4.5 mL of 37%) is heated at reflux for 8 hours. The reaction mixture is then cooled and treated with hydrochloric acid (10 mL of 4N) and evaporated to dryness. A portion of this residue is purified by HPLC to give 2,2,4-trimethyl-thiomorpholine-3-carboxylic acid, which is used as is. 2,2,4-Trimethyl-thiomorpholine-3-carboxylic acid (388 mg, 2.05 mmol) is stirred with dichloromethane (4 mL) and dimethylformamide (4 mL). To this is added (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (PyBOP, 1.07 g, 2.05 mmol). After 15 min, ethyl (2E,4S)-2,5-dimethyl-4-[methyl(3-methyl-L-valyl)amino]hex-2-enoate (0.640 g, 2.05 mmol, WO 99/32509) is added in dichlormethane (5 mL) followed by diisopropylethylamine (0.8 mL, 4.4 mmol). This is stirred at room temperature overnight. The reaction mixture is evaporated in vacuo and the residue treated with ethyl acetate and water. The ethyl acetate layer is dried over sodium sulfate, filtered and concentrated. The resulting material (314 mg, 0.65 mmol) is treated with aqueous 1M lithium hydroxide solution (3.3 mL, 3.3 mmol), water (1.6 mL) and methanol (6.5 mL), to provide the trifluoroacetic acid salt of the title compound as a white solid after preparative HPLC, MS (ES): m/z 456.29 (M+H).

1. temperatureis heated
2. temperatureat reflux for 8 hours
3. temperatureThe reaction mixture is then cooled
4. customevaporated to dryness
5. customA portion of this residue is purified by HPLC

ORD record

ord-147dbf593ea5443a970784d145552c05

Source dataset

uspto-grants-2009_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07626023B2