1,2-Dichloroethane → HCID 59556400, compound

6-Hydroxymethyl-benzo[b]thiophene-2-carboxylic acid ethyl ester (500 mg, 2.12 mmol) was dissolved in CH2Cl2 (10 mL) and Et3N (443 mL, 3.18 mmol) followed by mesyl chloride (197 mL, 2.54 mmol) were added. The solution was allowed to stir for 30 min and the solution was poured into 50 mL of Et2O. The organic solution was washed with 50 mL of 1 M KHSO4 followed by 50 mL of brine. The solution was dried over MgSO4 and the crude mesylate was used without further purification. This mesylate was dissolved in DMF (5 mL) and NaN3 (325 mg, 5.00 mmol) was added. The suspension was allowed to stir for 30 min then poured into 50 mL of water and 50 mL of EtOAc. The layers were separated then the organic solution was washed with 50 mL of brine and dried over MgSO4. The solution was concentrated to give the crude azide, which was used without further purification. The azide was dissolved in 8.80 mL of THF and 2.20 mL of MeOH and 2.20 mL of a 1 M solution of LiOH (2.20 mmol) was added. The solution was allowed to stir for 18 h, then diluted with 50 mL of EtOAc and washed with 50 mL of 1M KHSO4 followed by 50 mL of brine. The organic layer was dried and concentrated to give the crude acid that was used without further purification. This acid was dissolved in 4 mL of DMF. 1,2-phenylenediamine (459 mg, 4.24 mmol), EDC (810 mg, 4.24 mmol), and HOBT (573 mg, 4.24 mmol) were added and the solution was allowed to stir for 2 h. The solution was diluted with 50 mL of EtOAc and washed with 50 mL of water and 50 mL of brine. The organic solution was dried and concentrated then purified by flash chromatography (12-100% EtOAc in hexanes) to give the amide as a light yellow powder. 1H NMR (600 MHz, CDCl3) δ 4.49 (s, 2), 6.85 (t, 2, J=6.1), 7.10 (t, 1, J=7.4), 7.37 (t, 2, J=8.5), 7.82 (s, 1), 7.85 (d, 1, J=8.2), 7.90 (m, 2). MS cal'd 324 (MH+), exp 324 (MH+).

1. additionwere added
2. washThe organic solution was washed with 50 mL of 1 M KHSO4
3. dry with materialThe solution was dried over MgSO4
4. customthe crude mesylate was used without further purification
5. dissolutionThis mesylate was dissolved in DMF (5 mL)
6. stirringto stir for 30 min
7. customThe layers were separated
8. washthe organic solution was washed with 50 mL of brine
9. dry with materialdried over MgSO4
10. concentrationThe solution was concentrated
11. customto give the crude azide, which
12. customwas used without further purification
13. dissolutionThe azide was dissolved in 8.80 mL of THF
14. stirringto stir for 18 h
15. washwashed with 50 mL of 1M KHSO4
16. customThe organic layer was dried
17. concentrationconcentrated
18. customto give the crude acid that
19. customwas used without further purification
20. dissolutionThis acid was dissolved in 4 mL of DMF
21. stirringto stir for 2 h
22. washwashed with 50 mL of water and 50 mL of brine
23. customThe organic solution was dried
24. concentrationconcentrated
25. customthen purified by flash chromatography (12-100% EtOAc in hexanes)

ORD record

ord-f2798f5dd2aa47f6b98d3029d1626639

Source dataset

uspto-grants-2010_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07834034B2