Potassium Phosphate, Tribasic → N-[4-(2,4-difluorophenoxy)-3-[1-methyl-6-oxo-5-(2-trimethylsilylethynyl)pyridin-3-yl]phenyl]ethanesulfonamide

HRID 575763Notes

Reaction equation

HRID 575763 reaction equation
[CH3:1][N:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:5]=[C:4]([C:17]#[C:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[C:3]1=[O:23].Br[C:25]1[CH:26]=[C:27]([NH:40][S:41]([CH2:44][CH3:45])(=[O:43])=[O:42])[CH:28]=[CH:29][C:30]=1[O:31][C:32]1[CH:37]=[CH:36][C:35]([F:38])=[CH:34][C:33]=1[F:39].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:39][C:33]1[CH:34]=[C:35]([F:38])[CH:36]=[CH:37][C:32]=1[O:31][C:30]1[CH:25]=[CH:26][C:27]([NH:40][S:41]([CH2:44][CH3:45])(=[O:42])=[O:43])=[CH:28][C:29]=1[C:6]1[CH:5]=[C:4]([C:17]#[C:18][Si:19]([CH3:20])([CH3:21])[CH3:22])[C:3](=[O:23])[N:2]([CH3:1])[CH:7]=1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 117770988N-(3-bromo-4-(2,4-difluorophenoxy)phenyl)ethanesulfonamideHCID 1236063931-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(2-trimethylsilylethynyl)pyridin-2-one

Product 1

HCID 123739856N-[4-(2,4-difluorophenoxy)-3-[1-methyl-6-oxo-5-(2-trimethylsilylethynyl)pyridin-3-yl]phenyl]ethanesulfonamideYield 38.7%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(2-trimethylsilylethynyl)pyridin-2-one (200 mg, 0.6 mmol), N-[3-Bromo-4-(2,4-difluorophenoxy)phenyl]ethanesulfonamide (197 mg, 0.5 mmol), Pd(dppf)Cl2 (37 mg, 0.05 mmol) and K3PO4 (267 mg, 1.26 mmol) in dioxane (6 mL) and H2O (0.6 mL) was stirred at 70° C. under an atmosphere of argon for 12 h. After the mixture was concentrated, the residue was purified by column chromatography on silica gel (PE:EA=2:1) to give the title compound (100 mg, 38%) as a yellow solid. 1H NMR (CDCl3, 400 MHz): δ 7.82 (d, J=2.4 Hz, 1H), 7.67 (d, J=2.4 Hz, 1H), 7.23 (d, J=2.4 Hz, 1H), 7.16-7.12 (m, 1H), 6.99-6.91 (m, 2H), 6.87-6.83 (m, 1H), 6.78 (m, 1H), 6.65 (s, 1H), 3.61 (s, 3H), 3.14 (q, J=7.2 Hz, 2H), 1.42 (t, J=7.2 Hz, 3H), 024 (s, 9H). LCMS (M+H)+=517.

Workup

  1. concentrationAfter the mixture was concentrated
  2. customthe residue was purified by column chromatography on silica gel (PE:EA=2:1)

Sources & evidence

ORD record
ord-f42449eb42e644dba13c35b8efd5b1a7
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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