Reaktion #172789

Reaktionsgleichung

4-[(1S,5aR,5bR,7aS,9S,11aS,11bR,13aR,13bR)-3a-[[2-(1,1-dioxo-1,4-thiazinan-4-yl)acetyl]amino]-1-isopropyl-5a,5b,8,8,11a-pentamethyl-1,2,3,4,5,6,7,7a,9,10,11,11b,12,13,13a,13b-hexadecahydrocyclopenta[a]chrysen-9-yl]benzoate

TFA

lithium hydroxide monohydrate

→

4-((1S,3aS,5aR,5bR,7aS,9S,11aS,11bR,13aR,13bR)-3a-(((1,1-dioxido-4-thiomorpholinyl)acetyl)amino)-1-isopropyl-5a,5b,8,8,11a-pentamethylicosahydro-1H-cyclopenta[a]chrysen-9-yl)benzoic acid

TFA

Ausbeute 69.1%

Lösungsmittel

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Einengenthe reaction mixture was concentrated to dryness
2. 2
   workup.DISSOLUTIONThe crude residue was dissolved in THF (1.2 mL)
3. 3
   FiltrationThe resulting solution was filtered
4. 4
   Sonstigepurified

Vorschrift

To a solution of 4-[(1S,5aR,5bR,7aS,9S,11aS,11bR,13aR,13bR)-3a-[[2-(1,1-dioxo-1,4-thiazinan-4-yl)acetyl]amino]-1-isopropyl-5a,5b,8,8,11a-pentamethyl-1,2,3,4,5,6,7,7a,9,10,11,11b,12,13,13a,13b-hexadecahydrocyclopenta[a]chrysen-9-yl]benzoate, TFA (24.3 mg, 0.029 mmol) in THF (3 mL) was added a 0.753 molar aqueous solution of lithium hydroxide monohydrate (0.232 mL, 0.116 mmol). The reaction mixture was heated to 75° C. After 5.5 h, the reaction mixture was concentrated to dryness. The crude residue was dissolved in THF (1.2 mL), MeOH (0.3 mL) and 1N HCl (0.2 mL). The resulting solution was filtered and purified using prep HPLC method 3 to give 4-((1S,3aS,5aR,5bR,7aS,9S,11aS,11bR,13aR,13bR)-3a-(((1,1-dioxido-4-thiomorpholinyl)acetyl)amino)-1-isopropyl-5a,5b,8,8,11a-pentamethylicosahydro-1H-cyclopenta[a]chrysen-9-yl)benzoic acid, TFA (16.5 mg, 0.020 mmol, 69.1% yield) as a white solid. LCMS: m/z 709.6 (M+H+), retention time 2.072 min (method 6). 1H NMR (500 MHz, METHANOL-d4) δ=7.91 (d, J=8.2 Hz, 2H), 7.26 (d, J=8.2 Hz, 2H), 7.11 (s, 1H), 3.25-3.20 (m, 6H), 3.17 (d, J=5.5 Hz, 4H), 2.65-2.59 (m, 1H), 2.44 (dd, J=2.7, 13.1 Hz, 1H), 2.37 (dd, J=7.0, 12.5 Hz, 1H), 2.19-2.04 (m, 1H), 1.98-1.89 (m, 1H), 1.85 (d, J=13.1 Hz, 1H), 1.74 (dd, J=3.7, 7.9 Hz, 2H), 1.71-1.60 (m, 3H), 1.56-1.45 (m, 8H), 1.44-1.37 (m, 4H), 1.36-1.25 (m, 2H), 1.16-1.09 (m, 2H), 1.05 (s, 3H), 1.04 (s, 3H), 1.00 (s, 3H), 0.95 (d, J=2.1 Hz, 1H), 0.91 (d, J=6.7 Hz, 3H), 0.81 (d, J=6.7 Hz, 3H), 0.78 (s, 3H), 0.72 (s, 3H).

Quelle