Nitrogen → 5-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-3-methyl-1H-pyridin-2-one

HRID 518445Notes

Reaction equation

HRID 518445 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH3:9])[C:5](=[O:8])[NH:6][CH:7]=1.[CH:10]1([CH2:13][O:14][C:15]2[CH:20]=[CH:19][C:18]([S:21]([CH3:24])(=[O:23])=[O:22])=[CH:17][C:16]=2B2OC(C)(C)C(C)(C)O2)[CH2:12][CH2:11]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].N#N>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].CC(=O)OCC.C(Cl)Cl>[CH:10]1([CH2:13][O:14][C:15]2[CH:20]=[CH:19][C:18]([S:21]([CH3:24])(=[O:23])=[O:22])=[CH:17][C:16]=2[C:2]2[CH:3]=[C:4]([CH3:9])[C:5](=[O:8])[NH:6][CH:7]=2)[CH2:11][CH2:12]1

Participants

10

Reactant 4

HCID 947NitrogenHCID 62657Potassium Phosphate, TribasicHCID 2854365-Bromo-2-hydroxy-3-methylpyridineHCID 1234348592-[2-(Cyclopropylmethoxy)-5-(methylsulfonyl)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Product 1

HCID 1180216505-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-3-methyl-1H-pyridin-2-oneYield 58.8%

Reagents, catalysts & solvents 5

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

5-bromo-3-methyl-1H-pyridin-2-one (950 mg, 5.05 mmol), the title compound of Example 90, step 1 (2.93 g, 5.95 mmol), Pd(dppf)Cl2 (365 mg, 0.5 mmol) and K3PO4 (2.14 g, 10.1 mmol) in dioxane (30 mL) and water (5 mL) was purged with N2 and heated at 70° C. for 12 h. Silica gel chromatography (PE:DCM:EA=3:0:1 to 0:1:3) gave impure title compound (990 mg) as a yellow solid which was used directly in the next step. 1H NMR (CDCl3, 400 MHz) δ 12.57 (brs, 1H), 7.84 (d, J=8.8 Hz, 1H), 7.82 (s, 1H), 7.65 (s, 1H), 7.03 (d, J=8.8 Hz, 1H), 3.96 (d, J=7.2 Hz, 1H), 3.07 (s, 3H), 2.24 (s, 3H), 1.40-1.25 (m, 1H), 0.67-0.65 (m, 2H), 0.37-0.36 (m, 2H). LCMS: 334.1 (M+1)+

Sources & evidence

ORD record
ord-70080c35c0c549b8bb72e668df75b6c4
Source dataset
uspto-grants-2015_08
Patent number
US09115114B2

Reaction notes

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