Acetic Acid → 1-methylethyl [(cis)-1-acetyl-6-(4-{[(2-hydroxyethyl)amino]methyl}-1H-imidazol-1-yl)-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate

Dess-Martin periodinane (132 mg, 0.31 mmol) was added portionwise to a stirred suspension of 1-methylethyl {(cis)-1-acetyl-6-[4-(hydroxymethyl)-1H-imidazol-1-yl]-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl}carbamate (for a preparation see example 89) (100 mg, 0.26 mmol) in DCM (5 mL) and the resulting mixture was stirred at room temperature for 30 min. 5 mL of a saturated NaHCO3 aqueous solution was added and the mixture stirred for 15 min. The layers were separated and the aqueous phase was extracted with DCM (5 mL). The combined organic phases (DCM+AcOEt) were dried over MgSO4 and concentrated in vacuo. The residue was dissolved in DCM (5 mL) and Methanol (1 mL). Ethanolamine (63 mg, 1.03 mmol) and glacial acetic acid (15 mg, 15 μl, 0.26 mmol) were added. The reaction mixture was stirred at room temperature for 30 min then sodium triacetoxyborohydride (110 mg, 0.52 mmol) was added. The resulting mixture was stirred at room temperature for 16 h then treated with a saturated NaHCO3 aqueous solution. The layers were separated and the organic phase was washed with water, dried over MgSO4 and concentrated in vacuo. The residue was purified by MDAP (modifier: formic acid). The appropriate fractions were collected and concentrated in vacuo. The residue obtained was dissolved in water and the aqueous layer was basified with K2CO3 then extracted with DCM (4×10 mL). The combined organic phases were dried over MgSO4 and concentrated in vacuo to give 1-methylethyl[(cis)-1-acetyl-6-(4-{[(2-hydroxyethyl)amino]methyl}-1H-imidazol-1-yl)-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (13 mg, 0.030 mmol, 12%) as a colourless foam.

1. stirringthe mixture stirred for 15 min
2. customThe layers were separated
3. extractionthe aqueous phase was extracted with DCM (5 mL)
4. dry with materialThe combined organic phases (DCM+AcOEt) were dried over MgSO4
5. concentrationconcentrated in vacuo
6. dissolutionThe residue was dissolved in DCM (5 mL)
7. stirringThe reaction mixture was stirred at room temperature for 30 min
8. stirringThe resulting mixture was stirred at room temperature for 16 h
9. customThe layers were separated
10. washthe organic phase was washed with water
11. dry with materialdried over MgSO4
12. concentrationconcentrated in vacuo
13. customThe residue was purified by MDAP (modifier: formic acid)
14. customThe appropriate fractions were collected
15. concentrationconcentrated in vacuo
16. customThe residue obtained
17. extractionthen extracted with DCM (4×10 mL)
18. dry with materialThe combined organic phases were dried over MgSO4
19. concentrationconcentrated in vacuo

ORD record

ord-a04e2fff58d048c4904ec43b2084fb8f

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08697725B2