HCID 9843749, compound → LY 450139

Participants

Reaction Conditions

Reaction Steps

(2S)-2-hydroxy-3-methyl-N-[(1S)-1-methyl-2-oxo-2-[[(1S)-2,3,4,5-tetrahydro-3-methyl-2-oxo-1H-3-benzazepin-1-yl]amino]ethyl]-butanamide dihydrate (6 kg, 15.1 mol) is added to 55.2 L (9.2 volumes) of isopropyl alcohol. The mixture is heated to 70° C. to ensure dissolution. Once dissolved, the mixture is heated to reflux and 28 L (4.6 volumes) of solvent distilled, generating a saturated solution at reflux. The solution is seeded with 0.5% wt semagacestat (0.03 kg). The suspension is held for 1 h, followed by the addition of 36 L (6 volumes) of n-heptane (anti-solvent) added over 3 h. Distillation is used to remove an additional 33.6 L (5.6 vol) of solvent. The crystallizer is cooled from reflux (about 78° C.) to 25° C. over 2 h, held for 1, filtered, and dried. After drying, the isolated solids are milled with a Quadro Comil through a 230 μm round hole screen.

Provenance & Evidence