Hydrochloric Acid → Benzamide

Temperature

0 °C

3-Amino-N-(3,4-difluoro-phenyl)-4-methoxy-benzamide (2.0 g, 7.2 mmol) was dissolved in 50 mL of methylene chloride and cooled to 0° C. Chlorosulfonyl isocyanate (0.85 mL, 9.8 mmol) dissolved in 20 mL of methylene chloride was added dropwise. The mixture was stirred overnight. The resulting solid was collected by filtration and dried under vacuum. The dried solid (1.0 g, 2.4 mmol) was sited in 50 mL of methylene chloride with triethylamine (0.7 mL, 4.8 mmol) for 1 hour. Dimethylamine (1.2 mL of a 2N solution, 2.4 mmol) was added, and the solution stirred for 48 hours. The resulting mixture was washed with water (2×50 mL) and the organic phase dried over magnesium sulfate. The solvents were evaporated under reduced pressure to give a foam. The foam was redissolved in a small amount of fresh methylene chloride and treated with 1N hydrochloric acid (20 mL). Vigorous shaking produced a precipitate, which was collected via filtration. The resulting powder was sequentially triturated with water, methylene chloride, and ether. The triturated solid was dried under vacuum to give 0.64 g of benzamide, N-(3,4-difluorophenyl)-3-[[[[(dimethylamino)sulfonyl]-amino]carbonyl]amino]-4-methoxy-. Microanalysis: C17H18F2N4O5S-0.86 H2O; calculated: C=46.00; H=4.31; N=12.69. found: C=46.00; H=4.31; N=12.69. MS:M++1=349 Da. Mp 253-255° C. 1HNMR (400 MHz, DMSO-d6) δ 10.34 (s, 1H), 10.25 (s, 1H), 9.26 (s, 1H), 7.94-7.89 (m, 1H), 7.85 (d, J=8.7 Hz, 1H), 7.64 (s, 1H), 7.49-7.39 (m, 2H), 7.27 (d, J=8.4 Hz, 1H), 3.92 (s, 3H), 2.95 (s, 6H).

1. additionwas added dropwise
2. filtrationThe resulting solid was collected by filtration
3. customdried under vacuum
4. stirringthe solution stirred for 48 hours
5. washThe resulting mixture was washed with water (2×50 mL)
6. dry with materialthe organic phase dried over magnesium sulfate
7. customThe solvents were evaporated under reduced pressure
8. customto give a foam
9. stirringVigorous shaking
10. customproduced a precipitate, which
11. filtrationwas collected via filtration
12. customThe resulting powder was sequentially triturated with water, methylene chloride, and ether
13. customThe triturated solid was dried under vacuum

ORD record

ord-c35637d098cd4055aa1263ccf37fb581

Source dataset

uspto-grants-2005_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06906094B2