Ethyl Acetate → HCID 178517963, compound

Participants

Reaction Steps

To a 0° C. degassed THF (10 mL) solution containing 4-(cyclohexylamino)-8-(4-iodobenzyl)-1-(4-vinylphenyl)-1,3,8-triazaspiro[4.5]dec-3-en-2-one (860 mg, 1.5 mmol, Intermediate III.3.1b.1) was added 9-BBN (0.5 M THF, 6.0 mL, 3.0 mmol) dropwise. The vessel was warmed to rt and then heated at 70° C. for 40 min. Reaction was diluted with 290 mL degassed THF and 70 mL degassed 3.2 N NaOH. To the biphasic mixture Pd(PPh3)4 (346 mg, 0.3 mmol) was added and the reaction heated at 65° C. for 2 h. The mixture was cooled to rt and diluted with EtOAc (200 mL) and water (200 mL). The layers were separated and the aqueous layer extracted twice more with EtOAc. The organic layers were combined, washed with brine, dried over Na2SO4 and concentrated to give 2 g of crude material. Purification via flash silica chromatography using 10% MeOH in CH2Cl2 gave, upon solvent removal and further drying in vacuo, 546 mg of semi-pure material. Further purification via RP-HPLC (95/5 to 5/95 H2O/AcCN+0.1% TFA, YMC C18 column) gave two separable products, the first more polar product (15 mg) identified as the title example III.3.1c.1: 1H NMR (400 MHz, MeOD) δ 6.90 (dd, J=8.0, 2.0 Hz, 4H), 6.73 (dd, J=8.2, 2.0 Hz, 4H), 3.74 (m, 1H) 3.70 (s, 2H), 3.17 (m, 4H), 2.41 (bd, J=11.2 Hz, 2H), 2.07-1.92 (m, 7H), 1.80-1.65 (m, 6H), 1.39-1.30 (m, 4H); HRMS calc for C28H34N4O [M+H]+: 443.2806; measured: 443.2802

Provenance & Evidence