Methanol → 3-(but-3-ynyl)-5-tert-butylthiazol-2(3H)-imine

HRID 538797Notes

Reaction equation

HRID 538797 reaction equation
[C:1]([C:5]1[S:9][C:8]([NH2:10])=[N:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C(Cl)Cl.C[OH:15]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C=O)C>[NH4+:7].[OH-:15].[CH2:6]([N:7]1[CH:6]=[C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[S:9][C:8]1=[NH:10])[CH2:5][C:1]#[CH:2]

Participants

7

Reactant 3

HCID 887MethanolHCID 6344DichloromethaneHCID 6764855-tert-Butyl-1,3-thiazol-2-amine

Product 2

HCID 14923Ammonium HydroxideHCID 866234453-(but-3-ynyl)-5-tert-butylthiazol-2(3H)-imineYield 65%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of the product of Example 74A (0.20 g, 1.3 mmol), the product of Example 78A (0.29 g, 1.3 mmol), tetrabutylammonium iodide (0.24 g, 0.64 mmol) in DMF (1.5 mL) was warmed to 85° C. and stirred for 16 h. The mixture was cooled to ambient temperature and quenched with saturated aqueous NaHCO3 (5 mL) and diluted with EtOAc (10 mL). The layers were separated and the aqueous layer was extracted with EtOAc (2×5 mL). The combined organics were dried over anhydrous Na2SO4, filtered, concentrated under reduced pressure and purified via flash column chromatography (SiO2, 10% MeOH in EtOAc then 9:1:0.1 CH2Cl2:MeOH:NH4OH) to provide the title compound (0.18 g, 0.84 mmol, 65% yield). MS (DCI/NH3) m/z 209 (M+H)+.

Workup

  1. customquenched with saturated aqueous NaHCO3 (5 mL)
  2. additiondiluted with EtOAc (10 mL)
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc (2×5 mL)
  5. dry with materialThe combined organics were dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. custompurified via flash column chromatography (SiO2, 10% MeOH in EtOAc

Sources & evidence

ORD record
ord-bdaa21de51a2478d926f3be2baaacb60
Source dataset
uspto-grants-2014_10
Patent number
US08865753B2

Reaction notes

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