[(2R)-2-(cyclopentylmethyl)-3-(2-{5-fluoro-6-[(9aS)-hexahydropyrazino[2,1-c][1,4]oxazin-8(1H)-yl]-2-methyl-4-pyrimidinyl}hydrazino)-3-oxopropyl][(phenylmethyl)oxy]formamide → Lanopepden

HRID 1366418Notes

Reaction equation

HRID 1366418 reaction equation
[CH:1]1([CH2:6][C@@H:7]([C:20]([NH:22][NH:23][C:24]2[C:29]([F:30])=[C:28]([N:31]3[CH2:40][CH2:39][N:38]4[C@H:33]([CH2:34][O:35][CH2:36][CH2:37]4)[CH2:32]3)[N:27]=[C:26]([CH3:41])[N:25]=2)=[O:21])[CH2:8][N:9]([O:12]CC2C=CC=CC=2)[CH:10]=[O:11])[CH2:5][CH2:4][CH2:3][CH2:2]1>CO.[Pd]>[CH:1]1([CH2:6][C@@H:7]([C:20]([NH:22][NH:23][C:24]2[C:29]([F:30])=[C:28]([N:31]3[CH2:40][CH2:39][N:38]4[C@H:33]([CH2:34][O:35][CH2:36][CH2:37]4)[CH2:32]3)[N:27]=[C:26]([CH3:41])[N:25]=2)=[O:21])[CH2:8][N:9]([OH:12])[CH:10]=[O:11])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 1

HCID 86636930[(2R)-2-(cyclopentylmethyl)-3-(2-{5-fluoro-6-[(9aS)-hexahydropyrazino[2,1-c][1,4]oxazin-8(1H)-yl]-2-methyl-4-pyrimidinyl}hydrazino)-3-oxopropyl][(phenylmethyl)oxy]formamide

Product 1

HCID 52918384LanopepdenYield 78.1%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a solution of [(2R)-2-(cyclopentylmethyl)-3-(2-{5-fluoro-6-[(9aS)-hexahydropyrazino[2,1-c][1,4]oxazin-8(1H)-yl]-2-methyl-4-pyrimidinyl}hydrazino)-3-oxopropyl][(phenylmethyl)oxy]formamide (assumed 38.74 g, 68.0 mmol) in methanol (225 mL) was added 10% Pd/C (5.81 g). The mixture was hydrogenated under balloon pressure for 4 h, and was then filtered through a glass fiber filter with MeOH washes. The resulting solution was concentrated in vacuo to approximately 10% volume, diluted with EtOAc (400 mL), and concentrated in vacuo to approximately 30% volume. The resulting solid was collected by vacuum filtration and washed with EtOAc. The mother liquor and EtOAc washings were concentrated in vacuo to approximately 10% volume, and the resulting solid was collected by vacuum filtration and washed with EtOAc. The two crops of solid were combined and dried at 50° C. for 16 h under high vacuum to afford [(2R)-2-(cyclopentylmethyl)-3-(2-{5-fluoro-6-[(9aS)-hexahydropyrazino[2,1-c][1,4]oxazin-8(1H)-yl]-2-methyl-4-pyrimidinyl}hydrazino)-3-oxopropyl]hydroxyformamide (25.48 g, 78% yield for 2 steps) as a white solid. LCMS: (M+H)+: 480.1.

Workup

  1. filtrationwas then filtered through a glass fiber
  2. filtrationfilter with MeOH washes
  3. concentrationThe resulting solution was concentrated in vacuo to approximately 10% volume
  4. additiondiluted with EtOAc (400 mL)
  5. concentrationconcentrated in vacuo to approximately 30% volume
  6. filtrationThe resulting solid was collected by vacuum filtration
  7. washwashed with EtOAc
  8. concentrationThe mother liquor and EtOAc washings were concentrated in vacuo to approximately 10% volume
  9. filtrationthe resulting solid was collected by vacuum filtration
  10. washwashed with EtOAc
  11. customdried at 50° C. for 16 h under high vacuum

Sources & evidence

ORD record
ord-c3dc94b1c62d47988d5966e26be2245b
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

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