Cannabinoids ADB-PINACA Sintesis Video

[ireshop]

ADB-PINACA Synthesis

• G.Patton
• Sep 17, 2023
• 16

Video of ADB-PINACA Preparation from methyl 1H-indazole-3-carboxylate...

Methyl 1H-Indazole-3-carboxylate

1. A solution of indazole-3-carboxylic acid (100 g) in MeOH (1500 ml) was treated with concentrated H2SO4 (100 ml).
2. It was heated under reflux for 4 hours.
3. The mixture was concentrated under vacuum and dissolved in EtOAc (2500 ml).
4. The organic phase was washed with saturated aqueous NaHCO3 (1000 ml), H2O (1000 ml) and brine (1000 ml) and dried (MgSO4).
5. The solvent was evaporated under reduced pressure to give 83 g of a white solid.

Methyl 1-Pentyl-1H-indazole-3-carboxylate

1. To a cooled solution (0 °C) of methyl 1H-indazole-3-carboxylate (100 g) in THF (1000 ml) was added t-BuOK (70 g).
2. The mixture was warmed to room temperature, stirred for 1 hour, cooled (0 °C) and appropriate 1-bromopentane (80 ml) was added dropwise.
3. The mixture was warmed to room temperature and stirred for 48 hours, and H2O (1000 mL) was added.
4. The layers were separated, the aqueous layer was extracted with EtOAc (2x500 mL), and the combined organic phases were washed with H2O (3x500 mL) and brine (1000 mL) and dried (MgSO4).
5. The solvent was evaporated under reduced pressure to afford (67 g, 77%) as a clear glass-like solid.

1-Pentyl-1H-indazole-3-carboxylic acid

1. A solution of the appropriate methyl 1-pentyl-1H-indazole-3-carboxylate (100 g) in MeOH (1000 ml) was treated with 1M aqueous NaOH (600 ml) and stirred for 24 hours.
2. The solvent was reduced under vacuum, and the residue was dissolved in H2O, acidified with 1M aqueous HCl and extracted with EtOAc (2x500 ml).
3. The organic phase was dried (MgSO4), and the solvent was evaporated under reduced pressure to give the free acid, which was used in the subsequent coupling step without further purification, to yield (68 g, 72%) as a white solid.

ADB-PINACA ((S)-N-(1-Amino-3,3-dimethyl-1-oxobutan-2-yl)-1-pentyl-1H-indazole-3-carboxamide)

1. A solution of 1-Pentyl-1H-indazole-3-carboxylic acid (100 g) in DMF (1000 ml) was treated with EDC (1 equiv), BtOH (1.5 equiv), DIPEA (180 g), L-tert-leucinamide (86 g) and stirred for 24 hours.
2. The mixture was divided between H2O (2000 ml) and EtOAc (1000 ml), the layers were separated and the aqueous layer was extracted with EtOAc (2x1000 ml).
3. The combined organic phases were dried (MgSO4) and the solvent was evaporated under reduced pressure.
4. The crude products were purified by recrystallisation to give 92 g of a white solid (63% yield).