Water → HCID 58394277, compound

HRID 2047603Notes

Reaction equation

Cl[C:2]1[CH:3]=[C:4]([C:9]([C:12]2[S:13][CH:14]=[CH:15][N:16]=2)=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6].[CH3:17][C:18]1[CH:19]=[C:20](B(O)O)[CH:21]=[N:22][CH:23]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C=O)C.CCOC(C)=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].C(Cl)Cl>[CH3:17][C:18]1[CH:19]=[C:20]([C:2]2[CH:3]=[C:4]([C:5]([O:7][CH3:8])=[O:6])[C:9]([C:12]3[S:13][CH:14]=[CH:15][N:16]=3)=[CH:10][N:11]=2)[CH:21]=[N:22][CH:23]=1

Participants

Conditions

Temperature: 65 °C

Procedure

Methyl 2-chloro-5-(1,3-thiazol-2-yl)isonicotinate (7-2, 6.5 g, 26 mmol, 1 equiv), (5-methylpyridin-3-yl)boronic acid (3.8 g, 28 mmol, 1.1 equiv), cesium carbonate (29 g, 89 mmol, 3.5 equiv) and PdCl2(dppf)-CH2Cl2 adduct (4.2 g 5.1 mmol, 0.2 equiv) were suspended in DMF (102 mL) and water (4.6 mL, 255 mmol, 10 equiv). The reaction mixture was heated for 45 minutes at 65° C., diluted with EtOAc (200 mL) and filtered through celite. The organic layer was washed with water (2×200 mL), dried over MgSO4 and concentrated. The residue was purified by normal phase column chromatography (40-80% EtOAc in hexanes) to afford the title compound (7-3) as a tan solid. ESI+MS[M+H]+C16H14N3O2S=312.1

Workup

filtrationfiltered through celite
washThe organic layer was washed with water (2×200 mL)
dry with materialdried over MgSO4
concentrationconcentrated
customThe residue was purified by normal phase column chromatography (40-80% EtOAc in hexanes)

Sources & evidence

ORD record: ord-2e0ca82db71e489483ba7cd4854ade80
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08592457B2

Reaction notes

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