tert-Butanol → 4-(Biphenyl-2-ylamino)-2-fluoro-N-thiazol-2-yl-benzenesulfonamide

HRID 1644651Notes

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.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.[C:60]1([C:67]2[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=2)[C:61]([NH2:66])=[CH:62][CH:63]=[CH:64][CH:65]=1.CC(C)([O-])C.[Na+].C(O)(C)(C)C>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:60]1([C:67]2[CH:68]=[CH:69][CH:70]=[CH:71][CH:72]=2)[CH:65]=[CH:64][CH:63]=[CH:62][C:61]=1[NH:66][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

Participants

Conditions

Temperature: 120 °C

Procedure

Into a vial was added 4-bromo-2-fluoro-N-thiazol-2-yl-benzenesulfonamide (100 mg, 0.3 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (2.0 μl mg, 0.036 mmol), tris(dibenzylideneacetone)dipalladium(0) (11 mg, 0.012 mmol), [1,1′-Biphenyl]-2-amine (50.2 mg, 0.296 mmol), sodium tert-butoxide (86 mg, 0.89 mmol) and anhydrous tert-butyl alcohol (4.1 mL, 43 mmol). The reaction mixture was sparged with argon for ˜5 min. The septum was replaced with a microwave vial cap, and the reaction mixture was heated for 5 min at 120° C. The reaction mixture was then filtered through a syringe filter and the filtrate concentrated in vacuo. The vial and syringe were washed with 3 mL of DMSO and this was combined with the concentrated filtrate. The resulting solution was filtered through a plug of cotton then purified by reverse phase HPLC (Prep: Phenomenex 250×30.0 mm 15 micron C18 column. 40 mL/min. Gradient 15% B to 100% B over 25 min. Solvent A: 7800 water/200 acetonitrile/8 TFA. Solvent B: 7200 acetonitrile/800 water/8 TFA). The clean fractions were concentrated in vacuo to afford the product as an off-white solid. LC/MS analysis: Retention time: 1.52 minutes, M+H=426.

Workup

customThe reaction mixture was sparged with argon for ˜5 min
filtrationThe reaction mixture was then filtered through a syringe
filtrationfilter
concentrationthe filtrate concentrated in vacuo
washThe vial and syringe were washed with 3 mL of DMSO
filtrationThe resulting solution was filtered through a plug of cotton
customthen purified by reverse phase HPLC (Prep: Phenomenex 250×30.0 mm 15 micron C18 column. 40 mL/min. Gradient 15% B to 100% B over 25 min. Solvent A: 7800 water/200 acetonitrile/8 TFA. Solvent B: 7200 acetonitrile/800 water/8 TFA)
concentrationThe clean fractions were concentrated in vacuo

Sources & evidence

ORD record: ord-cc6c26b7714a414385420ebd81c4cf0e
Source dataset: uspto-grants-2012_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08124610B2

Reaction notes

Loading…