Methyl 5-iodo-6-oxo-1,6-dihydropyridine-3-carboxylate → methyl 6-oxo-5-(6-(trifluoromethyl)-1H-indazol-4-yl)-1,6-dihydropyridine-3-carboxylate

HRID 58092Notes

Reaction equation

CC1(C)C(C)(C)OB([C:9]2[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[C:14]3[C:10]=2[CH:11]=[N:12][NH:13]3)O1.I[C:24]1[C:29](=[O:30])[NH:28][CH:27]=[C:26]([C:31]([O:33][CH3:34])=[O:32])[CH:25]=1>O1CCOCC1.C([O-])(O)=O.[Na+].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]>[O:30]=[C:29]1[NH:28][CH:27]=[C:26]([C:31]([O:33][CH3:34])=[O:32])[CH:25]=[C:24]1[C:9]1[CH:17]=[C:16]([C:18]([F:19])([F:20])[F:21])[CH:15]=[C:14]2[C:10]=1[CH:11]=[N:12][NH:13]2

Participants

Conditions

Temperature: 140 °C

Procedure

A mixture of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6-(trifluoromethyl)-1H-indazole (43 mg, 0.138 mmol), methyl 5-iodo-6-oxo-1,6-dihydropyridine-3-carboxylate (38.4 mg, 0.138 mmol) and PdCl2(dppf) (5.04 mg, 6.89 μmol) in dioxane (2 mL) and aqueous saturated NaHCO3 solution (0.5 mL) was heated in a microwave reactor at 140° C. for 30 minutes. The reaction mixture was subsequently filtered and purified via preparative HPLC, eluting with a gradient of 20-90% ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA) to give the title compound as a white solid (7 mg, 15%). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.19 (s, 1H), 8.09-8.14 (m, 2H), 7.94 (s, 1H), 7.62 (s, 1H), 3.82 (s, 3H); ESI-MS m/z [M+H]+ calc'd for C15H10F3N3O3, 338.1. found 338.2.

Workup

filtrationThe reaction mixture was subsequently filtered
custompurified via preparative HPLC
washeluting with a gradient of 20-90% ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA)

Sources & evidence

ORD record: ord-9fccdc2395584eff9529e0145b172424
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09434743B2

Reaction notes

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