Cesium carbonate → 2-[5-(3-Amino-5-methylphenyl)-1,3-thiazol-2-yl]propane-2-sulfonamide

HRID 1039935Notes

Reaction equation

HRID 1039935 reaction equation
Br[C:2]1[S:6][C:5]([C:7]([S:10]([NH2:13])(=[O:12])=[O:11])([CH3:9])[CH3:8])=[N:4][CH:3]=1.[CH3:14][C:15]1[CH:16]=[C:17]([CH:19]=[C:20](B2OC(C)(C)C(C)(C)O2)[CH:21]=1)[NH2:18].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C(=O)([O-])[O-].[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH2:18][C:17]1[CH:19]=[C:20]([C:2]2[S:6][C:5]([C:7]([S:10]([NH2:13])(=[O:12])=[O:11])([CH3:9])[CH3:8])=[N:4][CH:3]=2)[CH:21]=[C:15]([CH3:14])[CH:16]=1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 672361713-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 672570342-(5-Bromothiazol-2-yl)propane-2-sulfonamide

Product 1

HCID 584563882-[5-(3-Amino-5-methylphenyl)-1,3-thiazol-2-yl]propane-2-sulfonamideYield 22.6%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
100 °C

Procedure

2-(5-Bromo-1,3-thiazol-2-yl)propane-2-sulfonamide (1.223 g, 4.29 mmol), 3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (1.00 g, 4.29 mmol), tris(dibenzylideneacetone)-dipalladium(0) (0.196 g, 0.214 mmol), X-phos (0.204 g, 0.429 mmol), and cesium carbonate (4.19 g, 12.87 mmol) were combined in a flask, sealed and purged with N2 (3×). Degassed dioxane (15 mL) and water (1.5 mL) were added and the reaction mixture was heated at 100° C. for 16 hrs. The reaction was diluted with water and extracted with EtOAc (2×). The combined organic layers were washed with brine, dried (MgSO4) and evaporated. Flash chromatography (SiO2, dry load, gradient elution 0 to 75% EtOAc in CH2Cl2) afforded 2-[5-(3-amino-5-methylphenyl)-1,3-thiazol-2-yl]propane-2-sulfonamide (0.302 g, 0.97 mmol, 22.6% yield) as a tan foam. MS ESI: [M+H]+ m/z 312.1. 1H NMR (500 MHz, DMSO-d6) δ 7.92 (s, 1H), 6.99 (m, 2H), 6.59 (m, 2H), 6.34 (s, 1H), 5.18 (br s, 2H), 2.15 (s, 3H), 1.75 (s, 6H).

Workup

  1. customsealed
  2. custompurged with N2 (3×)
  3. additionDegassed dioxane (15 mL) and water (1.5 mL) were added
  4. additionThe reaction was diluted with water
  5. extractionextracted with EtOAc (2×)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried (MgSO4)
  8. customevaporated
  9. dry with materialFlash chromatography (SiO2, dry load, gradient elution 0 to 75% EtOAc in CH2Cl2)

Sources & evidence

ORD record
ord-34659f40813b4e999e15af36bf010ef5
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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