Biphenyl → HCID 24986680, compound

Participants

Reaction Steps

2-(2-chloropyridin-4-yl)-5,6,7,8-tetrahydro-7,7-dimethylthiazolo[5,4-c]azepin-4-one (70 mg, 1.0 Eq.), 4-amino-N-methyl-benzamide (41 mg, 1.2 Eq.), NaOtBu (61 mg, 2.8 Eq.), Pd(OAc)2 (5 mg, 0.1 Eq.) were suspended/dissolved in dry toluene and degassed (vacuum/N2 cycles×5). 2-Di-tert-butylphosphino)biphenyl (143 mg, 0.2 Eq.) was then added. The resultant mixture was then refluxed overnight. A further portion of NaOtBu (61 mg, 2.8 Eq.), Pd(OAc)2 (5 mg, 0.1 Eq.) and 2-(di-tert-butylphosphino)biphenyl (14 mg, 0.2 Eq.) were added, followed by dry dioxane (0.5 mL). The resultant mixture was refluxed for a further night. The reaction mixture was allowed to cool to RT, partitioned between EtOAc/MeOH (3:1)/NH4Cl, and then extracted into EtOAc/MeOH (3:1) (3×50 mL). The combined organic layers were washed with brine (1×20 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. Purification was achieved using column chromatography (10% MeOH/90% DCM) to obtain the title compound as a bright yellow powder (18.6 mg, 19% yield); 1H NMR (DMSO D6) 1.0(6H, s), 2.8(3H, d), 3.0(2H, s), 3.0(2H, m), 7.3(1H, m), 7.5(1H, s), 7.8(4H, s), 8.2(1H, m), 8.3(2H, m), 9.6(1H, s); LC/MS M+1 (obs.) 422.20; LC/MS M−1 (obs.) 420.30.

Provenance & Evidence