Hydrochloric Acid → 4-{2-[2-(Acetylamino)-1,3-thiazol-4-yl]ethyl}-2-fluorobenzyl tert-butyl hydrazine-1,2-dicarboxylate

HRID 1892481Notes

Reaction equation

HRID 1892481 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH2:10][CH2:11][C:12]2[N:13]=[C:14]([NH:17][C:18](=[O:20])[CH3:19])[S:15][CH:16]=2)[CH:5]=[CH:6][C:7]=1[CH2:8][OH:9].[C:21]([N:28]1C=CN=C1)(N1C=CN=C1)=[O:22].[C:33]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])(=[O:36])[NH:34]N.Cl>O1CCCC1.COC(C)(C)C.CCCCCC.C(OCC)(=O)C.O>[NH:28]([C:21]([O:9][CH2:8][C:7]1[CH:6]=[CH:5][C:4]([CH2:10][CH2:11][C:12]2[N:13]=[C:14]([NH:17][C:18](=[O:20])[CH3:19])[S:15][CH:16]=2)=[CH:3][C:2]=1[F:1])=[O:22])[NH:34][C:33]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36]

Participants

10

Reactant 4

HCID 313Hydrochloric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 70091tert-Butyl carbazateHCID 86649988N-(4-{2-[3-fluoro-4-(hydroxymethyl)phenyl]ethyl}-1,3-thiazol-2-yl)acetamide

Product 1

HCID 866499894-{2-[2-(Acetylamino)-1,3-thiazol-4-yl]ethyl}-2-fluorobenzyl tert-butyl hydrazine-1,2-dicarboxylateYield 84.2%

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

To a suspension of N-(4-{2-[3-fluoro-4-(hydroxymethyl)phenyl]ethyl}-1,3-thiazol-2-yl)acetamide (118.8 mg, 0.4036 mmol) in anhydrous tetrahydrofuran (1.5 ml) was added 1,1′-carbonyldiimidazole (98.1 mg, 0.605 mmol), and the mixture was stirred at room temperature for 2.5 hr. tert-Butyl carbazate (160.3 mg, 1.213 mmol) was added, and the mixture was stirred at room temperature for 20 hr. Water, 1M hydrochloric acid and ethyl acetate were added, and the mixture was stirred, stood still and then partitioned. The organic layer was washed twice with water, and washed with saturated brine. After drying over anhydrous magnesium sulfate, the residue was concentrated under reduced pressure. The residue was suspended in dichloromethane (15 ml) and filtered. After washing with dichloromethane, the residue was dried under reduced pressure and purified by silica gel column chromatography (FUJI SILYSIA CHEMICAL LTD. BW-300SP 12 g, ethyl acetate:hexane=1:1). The fractions containing the object product were concentrated to give a solid, which was suspended in a mixture of tert-butyl methyl ether (5 ml) and hexane (5 ml) and filtered. The filtered product was dried under reduced pressure to give 4-{2-[2-(acetylamino)-1,3-thiazol-4-yl]ethyl}-2-fluorobenzyl tert-butyl hydrazine-1,2-dicarboxylate (153.7 mg, 0.340 mmol, yield 84.2%) as a white solid.

Workup

  1. stirringthe mixture was stirred at room temperature for 20 hr
  2. stirringthe mixture was stirred
  3. custompartitioned
  4. washThe organic layer was washed twice with water
  5. washwashed with saturated brine
  6. dry with materialAfter drying over anhydrous magnesium sulfate
  7. concentrationthe residue was concentrated under reduced pressure
  8. filtrationfiltered
  9. washAfter washing with dichloromethane
  10. customthe residue was dried under reduced pressure
  11. custompurified by silica gel column chromatography (FUJI SILYSIA CHEMICAL LTD. BW-300SP 12 g, ethyl acetate:hexane=1:1)
  12. additionThe fractions containing the object product
  13. concentrationwere concentrated
  14. customto give a solid, which
  15. filtrationfiltered
  16. customThe filtered product was dried under reduced pressure

Sources & evidence

ORD record
ord-627dda67749f4fd29c59dc434f3783da
Source dataset
uspto-grants-2013_08
Patent number
US08507690B2

Reaction notes

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