Potassium Phosphate, Tribasic → HCID 56848444, compound

HRID 1524249Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]([NH:11][C:12]1[S:13][C:14](Br)=[CH:15][N:16]=1)=[O:10].[F:18][C:19]1([F:38])[O:23][C:22]2[CH:24]=[C:25]([CH3:37])[C:26](B3OC(C)(C)C(C)(C)O3)=[CH:27][C:21]=2[O:20]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C(#N)C.O1CCOCC1.O.C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]([NH:11][C:12]1[S:13][C:14]([C:26]2[C:25]([CH3:37])=[CH:24][C:22]3[O:23][C:19]([F:18])([F:38])[O:20][C:21]=3[CH:27]=2)=[CH:15][N:16]=1)=[O:10]

Participants

Conditions

Temperature: 85 °C

Procedure

Argon was bubbled through a mixture of (2,6-difluorophenyl)-N-(5-bromo(1,3-thiazol-2-yl))carboxamide (152) (64 mg, 0.2 mmol), 2-(2,2-difluoro-6-methylbenzo[d][1,3]dioxol-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (489 mg, 0.3 mmol), bis(ditertbutyl(4-dimethylaminophenyl)phosphine)dichloropalladium (II) (21 mg, 10% mol) and K3PO4 (64 mg) in 1 mL ACN, 1 mL dioxane, 0.5 ml H2O. The reaction mixture was heated at 85° C. for 7 h. After cooling to room temperature, the reaction mixture was taken up in ethyl acetate, washed with aqueous NaHCO3 and brine. The organic phase was dried over (Na2SO4), concentrated and then subjected to prep HPLC chromatography to give (2,6-difluorophenyl)-N-[5-(2,2-difluoro-6-methylbenzo[d]1,3-dioxolen-5-yl)(1,3-thiazol-2-yl)]carboxamide (153) (7.4 mg, yield: 9%, purity>95%) as white solid. LC-MS: calcd. for C18H10F4N2O3S: 411 (M+1).

Workup

temperatureAfter cooling to room temperature
washwashed with aqueous NaHCO3 and brine
dry with materialThe organic phase was dried over (Na2SO4)
concentrationconcentrated

Sources & evidence

ORD record: ord-0bfb80ed5abe41fc8e28c96793a0f59a
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09079891B2

Reaction notes

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