Diisopropylethylamine → Ethyl 3-(4-cyanophenyl)-2,3-dihydro-imidazo[2,1-b]thiazole-5-carboxylate

HRID 844258Notes

Reaction equation

HRID 844258 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9](O)[CH2:10][S:11][C:12]2[NH:16][C:15]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:14][N:13]=2)=[CH:5][CH:4]=1)#[N:2].C(N(CC)C(C)C)(C)C.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O.CS(OS(C)(=O)=O)(=O)=O.C(=O)(O)[O-].[Na+]>C(Cl)Cl.CN(C=O)C>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:10][S:11][C:12]3=[N:13][CH:14]=[C:15]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[N:16]23)=[CH:5][CH:4]=1)#[N:2]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 81560Methanesulfonic anhydrideHCID 90495Di-tert-butyl dicarbonateHCID 516892Sodium BicarbonateHCID 22612527ethyl 2-[2-(4-cyanophenyl)-2-hydroxy-1-ethylthio]-3H-imidazole-4-carboxylate

Product 1

HCID 22612521Ethyl 3-(4-cyanophenyl)-2,3-dihydro-imidazo[2,1-b]thiazole-5-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of alcohol from Step B (6.95 g, 21.9 mmol) and N,N-diisopropylethylamine (11.4 mL, 65.7 mmol) in methylene chloride (300 mL)/DMF (50 mL) was added di-tert-butyl dicarbonate (6.69 g, 30.7 mmol) at 0° C. The reaction was stirred for 24 hours, then methanesulfonic anhydride (7.63 g, 43.8 mmol) was added in one portion. The reaction was stirred for 3 hours at 25° C. and 16 hours at reflux. The reaction was poured onto saturated aqueous sodium bicarbonate and extracted with methylene chloride (3×100 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo to provide a yellow oil. The crude product was purified by column chromatography (50→70% ethyl acetate/hexane) to provide the title compound as a yellow oil.

Workup

  1. stirringThe reaction was stirred for 3 hours at 25° C. and 16 hours
  2. temperatureat reflux
  3. extractionextracted with methylene chloride (3×100 mL)
  4. dry with materialThe combined organic layers were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto provide a yellow oil
  8. customThe crude product was purified by column chromatography (50→70% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-965b3cf68ad44cbbb1a0b611652e4c47
Source dataset
uspto-grants-2002_04
Patent number
US06380228B1

Reaction notes

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