Potassium Phosphate, Tribasic → (3,5-difluoro(4-pyridyl))-N-[5-(2,2-difluoro-6-methylbenzo[d]1,3-dioxolen-5-yl)(1,3-thiazol-2-yl)]carboxamide

HRID 1524248Notes

Reaction equation

HRID 1524248 reaction equation
[F:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([F:17])[C:7]=1[C:8]([NH:10][C:11]1[S:12][C:13](Br)=[CH:14][N:15]=1)=[O:9].[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:3]=[N:4][CH:5]=[C:6]([F:17])[C:7]=1[C:8]([NH:10][C:11]1[S:12][C:13]([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:14][N:15]=1)=[O:9]

Participants

8

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 584872352-(2,2-Difluoro-6-methylbenzo[d][1,3]dioxol-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 88576617(3,5-difluoro(4-pyridyl))-N-(5-bromo(1,3-thiazol-2-yl))carboxamide

Product 1

HCID 56848403(3,5-difluoro(4-pyridyl))-N-[5-(2,2-difluoro-6-methylbenzo[d]1,3-dioxolen-5-yl)(1,3-thiazol-2-yl)]carboxamideYield 40.8%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

Argon was bubbled through a mixture of (3,5-difluoro(4-pyridyl))-N-(5-bromo(1,3-thiazol-2-yl))carboxamide (148) (32 mg, 0.1 mmol), 2-(2,2-difluoro-6-methylbenzo[d][1,3]dioxol-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (45 mg, 0.15 mmol), bis(ditertbutyl(4-dimethylaminophenyl)phosphine)dichloropalladium (II) (11 mg, 10% mol) and K3PO4 (32 mg) in 1 mL ACN, 1 mL dioxane, 0.5 ml H2O. The reaction mixture was heated at 85° C. for 4 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 (Na2SO4), concentrated and then subjected to prep HPLC chromatography to give (3,5-difluoro(4-pyridyl))-N-[5-(2,2-difluoro-6-methylbenzo[d]1,3-dioxolen-5-yl)(1,3-thiazol-2-yl)]carboxamide (149) (16.8 mg, yield: 40.8%, purity>95%). LC-MS: calcd. for C17H9F4N3O3S: 412 (M+1).

Workup

  1. temperatureAfter cooling to room temperature
  2. washwashed with aqueous NaHCO3 and brine
  3. dry with materialThe organic phase was dried (Na2SO4)
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-0edfcf7ded654216b46f6dd2bdb09151
Source dataset
uspto-grants-2015_07
Patent number
US09079891B2

Reaction notes

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