Toluene → N-(2-amino-5-(thiophen-2-yl)phenyl)-4-(4-(2,3-dihydropyridin-2-yl)tetrahydropyran-4-yl)benzamide

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Reaction Steps

To 4-(4-cyano-tetrahydro-pyran-4-yl)-benzoic acid methyl ester (200 mg, 0.81 mmol) in toluene was added ethynyl-trimethyl-silane (800 mg, 10 eq) and CpCo(CO)2 (0.2 eq). The mixture was irradiated with light of 400 nm under stirring conditions for 2 days. Toluene was removed by evaporation. The solids were washed with water and the compound was extracted with EtOAc. The organic phase was dried and evaporated. 4-[4-(4,6-bis-trimethylsilanyl-pyridin-2-yl)-tetrahydro-pyran-4-yl]-benzoic acid methyl ester was dissolved in THF and TBAF was added in excess. The reaction mixture was stirred overnight at room temperature. After the reaction was done, it was extracted with EtOAc. The organic phase was evaporated to be used for next step. Hydrolysis, HATU coupling, and amine de-protection were carried out following the same procedures from Example 64 using (2-amino-4-thiophen-2-yl-phenyl)-carbamic acid tert-butyl ester instead of (3-amino-4′-fluoro-biphenyl-4-yl)-carbamic acid tert-butyl ester. MS found for C27H25N3O2S as (M+H)+ 456.26. 1H NMR (400 MHz, dmso-d6): δ: 9.59 (s, 1H), 8.51 (t, J=4.8 Hz, 1H), 7.87 (d, J=8.4 Hz, 2H), 7.70-7.66 (m, 1H), 7.47 (d, J=8.8 Hz, 2H), 7.39 (d, J=8.8 Hz, 2H), 7.30 (t, J=4.0 Hz, 1H), 7.24 (dd, J=8.4, 6.0 Hz, 1H), 7.18-7.14 (m, 2H), 7.01-6.99 (m, 1H), 6.75 (d, J=8.4 Hz, 1H), 5.09 (s, 2H), 3.64-3.67 (m, 2H), 3.58-3.46 (m, 2H), 2.72-2.69 (m, 2H), 2.34-2.29 (m, 2H).

Provenance & Evidence