Hydrochloric Acid → HCID 178432425, compound

HRID 2282274Notes

Reaction equation

HRID 2282274 reaction equation
Br[CH:2]([C:6]1[S:7][C:8]([C:17]2[N:21]=[CH:20][N:19](C3CCCCO3)[N:18]=2)=[C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[N:10]=1)[C:3]([CH3:5])=O.[NH2:28][C:29]1[S:30][CH:31]=[C:32]([CH3:34])[N:33]=1.Cl.[OH-].[Na+]>C1COCC1.CC(O)C>[CH3:34][C:32]1[N:33]2[C:2]([C:6]3[S:7][C:8]([C:17]4[N:21]=[CH:20][NH:19][N:18]=4)=[C:9]([C:11]4[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=4)[N:10]=3)=[C:3]([CH3:5])[N:28]=[C:29]2[S:30][CH:31]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 741432-Amino-4-methylthiazoleHCID 86649612HCID 86649612, compound

Product 1

HCID 178432425HCID 178432425, compoundYield 9.3%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 1-bromo-1-{4-phenyl-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-1,3-thiazol-2-yl}acetone (1.15 g, 2.5 mmol) obtained by similar manner with Example 116-B(vi) in THF (12.5 mL) and 2-propanol (12.5 mL), was added 2-amino-4-methylthiazole (1.43 g, 12.5 mmol), the mixture was stirred at 80° C. for 4 h. The reaction mixture was allowed to cool to 50° C., 2N hydrochloric acid (12.5 mL) was added, and the mixture was stirred for 12 h. The reaction mixture was allowed to cool to rt, and then neutralized by the addition of 2N aqueous sodium hydroxide solution (12.5 mL). The mixture was extracted with EtOAc (50 mL×2), and the combined organic layers were dried over anhydrous magnesium sulfate. Insoluble materials were removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (EtOAc/hexane=50/50→100/0; then MeOH/EtOAc=30/70) followed by silica gel column chromatography (EtOAc/hexane=30/70→100/0) to give the title compound (88 mg, 9%) as a yellow solid.

Workup

  1. temperatureto cool to 50° C.
  2. stirringthe mixture was stirred for 12 h
  3. temperatureto cool to rt
  4. extractionThe mixture was extracted with EtOAc (50 mL×2)
  5. dry with materialthe combined organic layers were dried over anhydrous magnesium sulfate
  6. customInsoluble materials were removed by filtration
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe residue was purified by basic silica gel column chromatography (EtOAc/hexane=50/50→100/0

Sources & evidence

ORD record
ord-49537e7fdfd748c6b9f590eb2016e443
Source dataset
uspto-grants-2015_09
Patent number
US09139589B2

Reaction notes

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