HCID 9843749, compound → LY 450139

HRID 2068499Notes

Reaction equation

HRID 2068499 reaction equation
O.O.[OH:3][C@@H:4]([CH:26]([CH3:28])[CH3:27])[C:5]([NH:7][C@@H:8]([CH3:25])[C:9](=[O:24])[NH:10][C@H:11]1[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=2[CH2:15][CH2:14][N:13]([CH3:22])[C:12]1=[O:23])=[O:6]>C(O)(C)C>[OH:3][C@@H:4]([CH:26]([CH3:28])[CH3:27])[C:5]([NH:7][C@@H:8]([CH3:25])[C:9](=[O:24])[NH:10][C@H:11]1[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=2[CH2:15][CH2:14][N:13]([CH3:22])[C:12]1=[O:23])=[O:6]

Participants

3

Reactant 1

HCID 9843749HCID 9843749, compound

Product 1

HCID 9843750LY 450139

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
70 °C

Procedure

(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.

Workup

  1. dissolutiondissolution
  2. dissolutionOnce dissolved
  3. temperaturethe mixture is heated
  4. temperatureto reflux
  5. distillation28 L (4.6 volumes) of solvent distilled
  6. temperatureat reflux
  7. additionfollowed by the addition of 36 L (6 volumes) of n-heptane (anti-solvent)
  8. additionadded over 3 h
  9. distillationDistillation
  10. customto remove an additional 33.6 L (5.6 vol) of solvent
  11. temperatureThe crystallizer is cooled
  12. temperaturefrom reflux (about 78° C.) to 25° C. over 2 h
  13. filtrationfiltered
  14. customdried
  15. customAfter drying
  16. customthe isolated solids are milled with a Quadro Comil through a 230 μm round hole screen

Sources & evidence

ORD record
ord-d33ab5f0021442e7bab68cc0788d316f
Source dataset
uspto-grants-2012_10
Patent number
US08299059B2

Reaction notes

Loading…