Hydrazine hydrate (1:1) → ethyl 5-{2-[(tert-butoxycarbonyl)amino]-2-methylpropyl}-1-(2-methoxyethyl)-1H-pyrazole-3-carboxylate

HRID 1984447

Reaction equation

HRID 1984447 reaction equation
[CH3:1][O:2][CH2:3][CH2:4]Br.[C:6]([O:10][C:11]([NH:13][C:14]([CH3:27])([CH3:26])[CH2:15][C:16]1[NH:20][N:19]=[C:18]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH:17]=1)=[O:12])([CH3:9])([CH3:8])[CH3:7].O.NN.C(O)(=O)C(O)=O.C(NN)CC.CC(C)([O-])C.[Na+]>C(O)C>[C:6]([O:10][C:11]([NH:13][C:14]([CH3:26])([CH3:27])[CH2:15][C:16]1[N:20]([CH2:4][CH2:3][O:2][CH3:1])[N:19]=[C:18]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH:17]=1)=[O:12])([CH3:8])([CH3:9])[CH3:7]

Participants

7

Reactant 5

HCID 24654Hydrazine hydrate (1:1)HCID 809722-Bromoethyl methyl ether2×HCID 96079Hydrazine, propyl-, ethanedioate (1:1)HCID 23676156Sodium t-butoxide2×HCID 66958447ethyl 5-{2-[(tert-butoxycarbonyl)amino]-2-methylpropyl}-1H-pyrazole-3-carboxylate

Product 1

HCID 66958319ethyl 5-{2-[(tert-butoxycarbonyl)amino]-2-methylpropyl}-1-(2-methoxyethyl)-1H-pyrazole-3-carboxylate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Under a nitrogen atmosphere, 2-bromoethyl methyl ether (19.7 g, 142 mmol) was added to a mixture of ethyl 5-{2-[(tert-butoxycarbonyl)amino]-2-methylpropyl}-1H-pyrazole-3-carboxylate (40 g, 129 mmol, prepared according to the method of Example 64 Part A using hydrazine hydrate in lieu of propylhydrazine oxalate) and sodium tert-butoxide (12.4 g, 129 mmol) in ethanol (128 mL). The reaction mixture was heated at reflux for 5 hours; an additional 0.2 equivalents of both sodium tert-butoxide and 2-bromoethyl methyl ether were added, and the reaction mixture was heated at reflux for an additional 21 hours. The reaction mixture was concentrated under reduced pressure and the residue was partitioned between water and tert-butyl methyl ether. The aqueous layer was extracted with tert-butyl methyl ether (×3). The combined organics were dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide 46.0 g of IFC (65 cartridge eluting with 1:1 tert-butyl methyl ether:hexanes) to provide a pale yellow oil. This material was triturated with 40 mL of 1:1 tert-butyl methyl ether:hexanes, seeded with product from an earlier run, stirred until a white solid formed, and then concentrated under reduced pressure to provide 24.83 g of ethyl 5-{2-[(tert-butoxycarbonyl)amino]-2-methylpropyl}-1-(2-methoxyethyl)-1H-pyrazole-3-carboxylate as a white solid, mp 92-93° C. MS (APCI) m/z 370 (M+H)+; Anal. Cacld for C18H31 N3O5: C, 58.52; H, 8.46; N, 11.37. Found: C, 58.65; H. 8.69; N, 11.47.

Workup

  1. customprepared
  2. temperatureThe reaction mixture was heated
  3. temperatureat reflux for 5 hours
  4. temperaturethe reaction mixture was heated
  5. temperatureat reflux for an additional 21 hours
  6. concentrationThe reaction mixture was concentrated under reduced pressure
  7. customthe residue was partitioned between water and tert-butyl methyl ether
  8. extractionThe aqueous layer was extracted with tert-butyl methyl ether (×3)
  9. dry with materialThe combined organics were dried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customto provide
  13. wash46.0 g of IFC (65 cartridge eluting with 1:1 tert-butyl methyl ether:hexanes)
  14. customto provide a pale yellow oil
  15. customThis material was triturated with 40 mL of 1:1 tert-butyl methyl ether
  16. customformed
  17. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b26246f9c5374e8daf7ee452af09a65d
Source dataset
uspto-grants-2009_06
Patent number
US07544697B2

Linked notes

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