Hydrazine hydrate (1:1) → (9aS)-8-(5-fluoro-6-hydrazino-2-methyl-4-pyrimidinyl)octahydropyrazino[2,1-c][1,4]oxazine

HRID 1366416Notes

Reaction equation

HRID 1366416 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([N:9]2[CH2:18][CH2:17][N:16]3[C@H:11]([CH2:12][O:13][CH2:14][CH2:15]3)[CH2:10]2)[C:3]=1[F:19].O.[NH2:21][NH2:22]>O1CCOCC1>[F:19][C:3]1[C:4]([N:9]2[CH2:18][CH2:17][N:16]3[C@H:11]([CH2:12][O:13][CH2:14][CH2:15]3)[CH2:10]2)=[N:5][C:6]([CH3:8])=[N:7][C:2]=1[NH:21][NH2:22]

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 866369294-[(9aS)-octahydropyrazino[2,1-c][1,4]oxazin-8-yl]-6-chloro-5-fluoro-2-methylpyrimidine

Product 1

HCID 66936132(9aS)-8-(5-fluoro-6-hydrazino-2-methyl-4-pyrimidinyl)octahydropyrazino[2,1-c][1,4]oxazineYield 92%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of (9aS)-8-(6-chloro-5-fluoro-2-methyl-4-pyrimidinyl)octahydropyrazino[2,1-c][1,4]oxazine (assumed 31.03 g, 108.2 mmol) in dioxane (430 mL) was added hydrazine monohydrate (31 mL). The mixture was heated and stirred at 80° C. overnight, and then at 85° C. for 7 h. The mixture was cooled to room temperature and concentrated in vacuo. The residue was dissolved in DCM (500 mL) and washed with saturated aq. NaHCO3 (200 mL). The aqueous phase was extracted with a fresh portion of DCM (100 mL), and this organic phase was washed with saturated aq. NaHCO3 (100 mL). The combined organic phase was dried over anhydrous Na2SO4, filtered, concentrated in vacuo, and dried under high vacuum overnight to provide (9aS)-8-(5-fluoro-6-hydrazino-2-methyl-4-pyrimidinyl)octahydropyrazino[2,1-c][1,4]oxazine (27.98 g, 92% yield for 2 steps) as a light yellow solid. LCMS: (M+H)+: 283.3.

Workup

  1. temperatureThe mixture was heated
  2. waitat 85° C. for 7 h
  3. temperatureThe mixture was cooled to room temperature
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was dissolved in DCM (500 mL)
  6. washwashed with saturated aq. NaHCO3 (200 mL)
  7. extractionThe aqueous phase was extracted with a fresh portion of DCM (100 mL)
  8. washthis organic phase was washed with saturated aq. NaHCO3 (100 mL)
  9. dry with materialThe combined organic phase was dried over anhydrous Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customdried under high vacuum overnight

Sources & evidence

ORD record
ord-2abc7b5d59674e2b97d60bec4cafd870
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

Loading…