1,4-Dioxane → 4-(4-Tert-butyl-thiazol-2-ylamino)-2-fluoro-N-thiazol-2-yl-benzenesulfonamide

HRID 1644634Notes

Reaction equation

HRID 1644634 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12]2[S:13][CH:14]=[CH:15][N:16]=2)(=[O:10])=[O:9])=[C:4]([F:17])[CH:3]=1.CC(C)([O-])C.[Na+].[CH3:24][C:25]1([CH3:65])[C:38]2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)[C:33]=2OC2[C:26]1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.[NH2:66][C:67]1[S:68]C=C(C2C=CC(Cl)=CC=2)[N:71]=1.O1CCOCC1>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]>[C:25]([C:38]1[N:66]=[C:67]([NH:71][C:2]2[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12]3[S:13][CH:14]=[CH:15][N:16]=3)(=[O:10])=[O:9])=[C:4]([F:17])[CH:3]=2)[S:68][CH:33]=1)([CH3:65])([CH3:26])[CH3:24]

Participants

7

Reactant 5

HCID 312751,4-DioxaneHCID 732412-Amino-4-(4-chlorophenyl)thiazoleHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 251383534-Bromo-2-fluoro-N-thiazol-2-yl-benzenesulfonamide

Product 1

HCID 252040274-(4-Tert-butyl-thiazol-2-ylamino)-2-fluoro-N-thiazol-2-yl-benzenesulfonamideYield 40%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
150 °C

Procedure

Into a vial was added the 4-bromo-2-fluoro-N-thiazol-2-yl-benzenesulfonamide (50 mg, 0.0001 mol), sodium tert-butoxide (43 mg, 0.00044 mol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (1.0E1 mg, 0.000018 mol), tris(dibenzylideneacetone)dipalladium(0) (5.4 mg, 0.0000059 mol), 2-amino-4-(4-chlorophenyl)thiazole and the de-gassed anhydrous 1,4-dioxane (2.0 mL, 0.026 mol). The reaction mixture was heated at 150° C. for 1 h in microwave. The reaction mixture was filtered through celite and the filtrate was concentrated. The residue was diluted with EtOAc and washed with 1.0 N HCl, dried and was concentrated to give the crude product that was purified using Gilson preparative HPLC (reverse phase, Phenomenex 250×30 mm, 15 micron C18 column, 40 mL/min. Gradient, 85% A to 100% B over 25 min. Solvent A: 7800 water/200 acetonitrile/8 TFA. Solvent B: 7200 acetonitrile/800 water/8). Fractions were checked by LC/MS, then combined, and dried on a lyophilizer to give the product as a yellow solid (24.5 mg, 40%).

Workup

  1. filtrationThe reaction mixture was filtered through celite
  2. concentrationthe filtrate was concentrated
  3. additionThe residue was diluted with EtOAc
  4. washwashed with 1.0 N HCl
  5. customdried
  6. concentrationwas concentrated
  7. customto give the crude product that
  8. customwas purified
  9. customGilson preparative HPLC (reverse phase, Phenomenex 250×30 mm, 15 micron C18 column, 40 mL/min. Gradient, 85% A to 100% B over 25 min. Solvent A: 7800 water/200 acetonitrile/8 TFA. Solvent B: 7200 acetonitrile/800 water/8)
  10. customdried on a lyophilizer

Sources & evidence

ORD record
ord-3c6ebedf6af54b0cb1e7276f6b620f3e
Source dataset
uspto-grants-2012_02
Patent number
US08124610B2

Reaction notes

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