Potassium Phosphate, Tribasic → US10023592, Example 381

HRID 518544Notes

Reaction equation

Br[C:2]1[C:3]([O:14][CH2:15][CH:16]2[CH2:18][CH2:17]2)=[CH:4][C:5](=[O:13])[N:6]([CH2:8][S:9]([CH3:12])(=[O:11])=[O:10])[CH:7]=1.[CH3:19][N:20]1[CH:25]=[C:24](B2OC(C)(C)C(C)(C)O2)[CH:23]=[CH:22][C:21]1=[O:35].[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:16]1([CH2:15][O:14][C:3]2[C:2]([C:24]3[CH:23]=[CH:22][C:21](=[O:35])[N:20]([CH3:19])[CH:25]=3)=[CH:7][N:6]([CH2:8][S:9]([CH3:12])(=[O:11])=[O:10])[C:5](=[O:13])[CH:4]=2)[CH2:18][CH2:17]1

Participants

Conditions

Temperature: 70 °C

Procedure

The title compound from step 4 (50 mg, 0.15 mmol), 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-one (42 mg, 0.18 mmol), Pd(dppf)Cl2 (11 mg, 14.9 umol) and K3PO4 (63 mg, 0.3 mmol) in dioxane (5 mL) and water (5 drops) were degassed and then heated to 70° C. under N2 overnight. The reaction mixture was then concentrated under reduced pressure. The residue was purified by column chromatography (PE:DCM:EA=3:0:1 to 0:1:4) followed by preparative HPLC to afford the title compound (17.09 mg, 31.5%) as an off-white solid. 1H NMR (CDCl3, 400 MHz) δ 7.50 (dd, J1=9.2 Hz, J2=2.4 Hz, 1H), 7.43 (d, J=2.4 Hz, 1H), 6.71 (d, J=9.2 Hz, 1H), 5.96 (s, 1H), 5.16 (s, 2H), 3.86 (d, J=6.8 Hz, 1H), 3.63 (s, 3H), 2.99 (s, 3H), 1.26-1.21 (m, 1H), 0.70-0.66 (m, 2H), 0.36-0.32 (m, 2H). LCMS: 365.0 (M+1)+

Workup

concentrationThe reaction mixture was then concentrated under reduced pressure
customThe residue was purified by column chromatography (PE:DCM:EA=3:0:1 to 0:1:4)

Sources & evidence

ORD record: ord-8af9d14cfcc14859a5672655846e4390
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09115114B2

Reaction notes

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