Diisopropylethylamine → HCID 178425695, compound

HRID 1893717Notes

Reaction equation

HRID 1893717 reaction equation
Br[C:2]1[N:3]=[C:4]([O:7][C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH3:14])[N:9]=2)[S:5][CH:6]=1.[CH3:15][C:16]1[C:20](B2OC(C)(C)C(C)(C)O2)=[CH:19][NH:18][N:17]=1.C(N(C(C)C)C(C)C)C>O1CCOCC1.O.[Pd].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:15][C:16]1[C:20]([C:2]2[N:3]=[C:4]([O:7][C:8]3[CH:13]=[CH:12][CH:11]=[C:10]([CH3:14])[N:9]=3)[S:5][CH:6]=2)=[CH:19][NH:18][N:17]=1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 66871773HCID 66871773, compoundHCID 178434487HCID 178434487, compound2×

Product 1

HCID 178425695HCID 178425695, compoundYield 26%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
120 °C

Procedure

According to Scheme 4: A mixture of 2-(4-bromothiazol-2-yloxy)-6-methylpyridine (0.37 mmol, 100 mg), 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.44 mmol, 92 mg), Pd (dppf) (37 μmol, 30 mg) and N-ethyl-N-isopropylpropan-2-amine (0.74 mmol, 0.13 mL) in dioxane/water (1:1, 2.5 mL) was stirred at 120° C. for 1 hour under microwave conditions. To complete the reaction, PdCl2(dppf) (37 μmol, 30 mg) and 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.44 mmol, 92 mg) were added and the reaction mixture was stirred at 120° C. for 1.5 hour under microwave conditions. The reaction mixture was filtered through a pad of celite and was washed with DCM. The organic phase was washed with water, was dried over MgSO4, was filtered and was concentrated under reduced pressure. The crude mixture was purified by flash chromatography over silica gel using DCM/EtOH/NH3 (100:0:0 to 93:6.4:0.6) as eluent to yield 4-(3-methyl-1H-pyrazol-4-yl)-2-(6-methylpyridin-2-yloxy)thiazole (95 μmol, 26 mg, 26%) as an orange solid.

Workup

  1. additionwere added
  2. stirringthe reaction mixture was stirred at 120° C. for 1.5 hour under microwave conditions
  3. filtrationThe reaction mixture was filtered through a pad of celite
  4. washwas washed with DCM
  5. washThe organic phase was washed with water
  6. dry with materialwas dried over MgSO4
  7. filtrationwas filtered
  8. concentrationwas concentrated under reduced pressure
  9. customThe crude mixture was purified by flash chromatography over silica gel

Sources & evidence

ORD record
ord-b6a640e0f32a4b3f8b8511419b46d79f
Source dataset
uspto-grants-2013_08
Patent number
US08513252B2

Reaction notes

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