Acetic Acid → HCID 178472272, compound

To a solution of compound 17 (148 mg, 0.240 mmol) in 4 mL of Methanol was added (1,2,3,4-Tetrahydro-isoquinolin-6-ylmethyl)-phosphonic acid diethyl ester (70.0 mg, 0.240 mmol), acetic acid (43.0 μL, 0.720 mmol). The reaction mixture was stirred for 3 minutes, followed by addition of Sodium Cyanoborohydride (75.3 mg, 1.20 mmol). The reaction mixture was stirred at 25° C. for 14 hours. The reaction mixture was diluted with EtOAc and washed with H2O (3×), brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified using silica gel chromatography (CH2Cl2/Isopropanol=100/5) to give 59 mg of TES protected intermediate. 83 μL of 48% HF solution was added to acetonitrile (4 mL) to prepare the 2% HF solution. The above 2% HF solution was added to TES protected intermediate (47 mg, 0.053 mmol) and the reaction mixture was stirred for 2 hours. The solvent was concentrated and the residue was diluted with EtOAc, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified using silica gel chromatography (CH2Cl2/Methanol=100/10) to give 35.2 mg of compound 18: 1H NMR (CDCl3) δ 7.73 (2H, d, J=8.9 Hz), 7.05 (2H, m), 6.89 (2H, m), 6.76 (1H, m), 5.75 (1H, m), 5.67 (1H, m), 5.3 (2H, m), 4.2-3.6 (12H, m), 3.4-2.4 (11H, m), 2.1-1.8 (6H, m), 1.4-1.28 (8H, m), 0.92 (6H, m).

1. stirringThe reaction mixture was stirred at 25° C. for 14 hours
2. washwashed with H2O (3×), brine
3. dry with materialdried over sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. customThe residue was purified
7. customto give 59 mg of TES
8. customto prepare the 2% HF solution
9. additionThe above 2% HF solution was added to TES
10. stirringthe reaction mixture was stirred for 2 hours
11. concentrationThe solvent was concentrated
12. additionthe residue was diluted with EtOAc
13. dry with materialdried over sodium sulfate
14. filtrationfiltered
15. concentrationconcentrated under reduced pressure
16. customThe residue was purified

ORD record

ord-002a8405d4ce45dbba38b36654ba7075

Source dataset

uspto-grants-2010_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07649015B2