Hydrochloric Acid → HCID 18322369, compound

Temperature

0 °C

A slurry of methylamine hydrochloride (9.51 g, 141 mmol, 3.1 equiv) in anh. toluene (600 mL) at 0° C. was treated with AlMe3 (2M in toluene, 70 mL, 141 mmol, 3.1 equiv) over 10 min. The resulting solution was stirred at 0° C. for 1 h then allowed to warm to room temp. and stirred for 40 min. Methyl 3-amino-5-tert-butylthiophene-2-carboxylate (9.87 g, 46 mmol) was added to the aluminum amide solution. The resulting mixture was heated at the reflux temp. for 3 d, cooled to 0° C., and a 6N HCl solution was added dropwise. The quenched mixture was made basic with a 20% KOH solution (95 mL). The resulting slurry was partitioned between H2O (300 mL) and EtOAc (300 mL) and the aqueous layer was extracted with EtOAc (3×300 mL). The combined organic layers were dried (Na2SO4) and concentrated under reduced pressure to afford N-methyl-3-amino-5-tert-butylthiophene-2-carboxamide as a green-yellow solid (9.47 g, 97%): mp 230-1° C.; TLC (20% EtOAc/CH2Cl2) Rf0.23; 1H NMR (d6-DMSO) δ1.28 (s, 9H), 2.63 (d, J=4.8 Hz, 3H), 6.29 (br s, 2H), 6.37 (d, J=1.1 Hz, 1H), 7.22 (q, J=4.0 Hz, 1H).

1. temperatureto warm to room temp.
2. stirringstirred for 40 min
3. temperatureThe resulting mixture was heated at the reflux temp
4. waitfor 3 d
5. temperaturecooled to 0° C.
6. customThe resulting slurry was partitioned between H2O (300 mL) and EtOAc (300 mL)
7. extractionthe aqueous layer was extracted with EtOAc (3×300 mL)
8. dry with materialThe combined organic layers were dried (Na2SO4)
9. concentrationconcentrated under reduced pressure

ORD record

ord-9b352f9cfb9f42f8a86def2e3548e83e

Source dataset

uspto-grants-2002_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06344476B1