Potassium Phosphate, Tribasic → 5-[2-(Cyclopropylmethoxy)-5-ethylsulfonylphenyl]-3-hydroxy-1-methylpyridin-2-one

HRID 575766Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([OH:10])[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[CH:11]1([CH2:14][O:15][C:16]2[CH:21]=[CH:20][C:19]([S:22]([CH2:25][CH3:26])(=[O:24])=[O:23])=[CH:18][C:17]=2B2OC(C)(C)C(C)(C)O2)[CH2:13][CH2:12]1.[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]>[CH:11]1([CH2:14][O:15][C:16]2[CH:21]=[CH:20][C:19]([S:22]([CH2:25][CH3:26])(=[O:24])=[O:23])=[CH:18][C:17]=2[C:2]2[CH:3]=[C:4]([OH:10])[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=2)[CH2:12][CH2:13]1

Participants

Conditions

Temperature: 90 °C

Procedure

To a mixture of 5-bromo-3-hydroxy-1-methylpyridin-2-one (1.00 g, 4.9 mmol), 2-[2-(cyclopropylmethoxy)-5-ethylsulfonylphenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.80 g, 4.9 mmol) in dioxane (30 mL) and H2O (5 mL) was added K3PO4 (3.12 g, 14.7 mmol), Pd(dppf)Cl2 (358 mg, 0.49 mmol). After purging the mixture with nitrogen, the mixture was stirred at 90° C. under microwave irradiation for 1 h. After the mixture was filtered, the filtrate was concentrated to dryness. The resulting residue was purified by prep-HPLC to give the title compound (0.9 g, 51%) as a purple solid. 1H NMR (CDCl3, 400 MHz) δ 7.81 (dd, J1=8.8 Hz, J2=2.4 Hz, 1H), 7.77 (d, J=2.4 Hz, 1H), 7.16-7.15 (m, 2H), 3.95 (d, J=6.8 Hz, 2H), 3.70 (s, 3H), 3.12 (q, J=7.6 Hz, 2H), 1.32-1.27 (m, 4H), 0.70-0.67 (m, 2H), 0.39-0.36 (m, 2H). LCMS (M+H)+=364.

Workup

customAfter purging the mixture with nitrogen
filtrationAfter the mixture was filtered
concentrationthe filtrate was concentrated to dryness
customThe resulting residue was purified by prep-HPLC

Sources & evidence

ORD record: ord-6d26192bbf3740c6abd9ee2bcf517699
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09034900B2

Reaction notes

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