Tetrahydrofuran → Ethyl 2-(2-acetamidopyridin-4-yl)-4-(naphthalen-2-ylmethyl)thiazole-5-carboxylate

HRID 2401846Notes

Reaction equation

HRID 2401846 reaction equation
[C:1]([NH:4][C:5]1[CH:10]=[C:9]([C:11]2[S:12][C:13]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[C:14](Br)[N:15]=2)[CH:8]=[CH:7][N:6]=1)(=[O:3])[CH3:2].[Br-].[CH:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:26]=[CH:25][C:24]=1[CH2:33][Zn+].C1COCC1>CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[C:1]([NH:4][C:5]1[CH:10]=[C:9]([C:11]2[S:12][C:13]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[C:14]([CH2:33][C:24]3[CH:25]=[CH:26][C:27]4[C:32](=[CH:31][CH:30]=[CH:29][CH:28]=4)[CH:23]=3)[N:15]=2)[CH:8]=[CH:7][N:6]=1)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 66747706Ethyl 2-(2-acetamidopyridin-4-yl)-4-bromothiazole-5-carboxylateHCID 178419770HCID 178419770, compound2×

Product 1

HCID 66747854Ethyl 2-(2-acetamidopyridin-4-yl)-4-(naphthalen-2-ylmethyl)thiazole-5-carboxylateYield 40%

Reagents, catalysts & solvents 1

HCID 178418851HCID 178418851, compoundCatalyst2×

Procedure

To a mixture of ethyl 2-(2-acetamidopyridin-4-yl)-4-bromothiazole-5-carboxylate (190 mg, 0.510 mmol) and bis(tri-t-butylphosphine)palladium(0) (65.6 mg, 0.128 mmol) under nitrogen was added a 0.500 M solution of 2-napthylmethylzinc bromide in THF (3.60 mL, 1.80 mmol). The reaction was stirred at room temperature for 5 minutes, then at 60 degrees for 1 hour. Another portion of bis(tri-t-butylphosphine)palladium(0) (60.0 mg, 0.117 mmol) was added, followed by another portion of 0.500 M solution of 2-napthylmethylzinc bromide in THF (3.00 mL, 1.50 mmol), and the reaction was heated at 60 degrees for an additional 45 minutes. The reaction was cooled to room temperature and quenched with saturated ammonium chloride (10 mL). The mixture was extracted with ethyl acetate (2×20 mL) and the combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (ethyl acetate/hexane=0/100→100/0) to give 100 mg of the title compound. (40% yield). LC/MS (FA) ES+ 432.

Workup

  1. waitat 60 degrees for 1 hour
  2. temperaturethe reaction was heated at 60 degrees for an additional 45 minutes
  3. temperatureThe reaction was cooled to room temperature
  4. customquenched with saturated ammonium chloride (10 mL)
  5. extractionThe mixture was extracted with ethyl acetate (2×20 mL)
  6. dry with materialthe combined organic layers were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by silica gel chromatography (ethyl acetate/hexane=0/100→100/0)

Sources & evidence

ORD record
ord-4f4dc40df5b841ac8a03d2111e5c52c8
Source dataset
uspto-grants-2014_08
Patent number
US08796268B2

Reaction notes

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