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

HRID 518496Notes

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 irridation 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-1a46733cde5442fcbef593de32434b01
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09115114B2

Reaction notes

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