tert-butyl (2S,4R)-2-[(4-amino-2-methoxyphenoxy)methyl]4-hydroxypyrrolidine-1-carboxylate → tert-butyl (2S,4R)-2-({4-[6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3(4H)-yl]-2-methoxyphenoxy}methyl)-4-hydroxypyrrolidine-1-carboxylate

Participants

Reaction Steps

Methyl 5-(4-chlorophenyl)-3-{[(E)-(dimethylamino)methylidene]amino}-2-thiophenecarboxylate (857 mg, 2.66 mmol) was mixed with tert-butyl (2S,4R)-2-[(4-amino-2-methoxyphenoxy)methyl]4-hydroxypyrrolidine-1-carboxylate (900 mg) in phenol (1.0 g) at 120° C. for 15 min. Workup and purification of the reaction mixture provided 650 mg of tert-butyl (2S,4R)-2-({4-[6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3(4H)-yl]-2-methoxyphenoxy}methyl)-4-hydroxypyrrolidine-1-carboxylate. A portion of this material (105 mg, 0.179 mmol) was dissolved in a 1:1 mixture of dichloromethane and trifluoroacetic acid. The mixture was stirred at room temperature for 10 min and was then concentrated under reduced pressure. The residue was dissolved in dichloromethane and washed with a saturated solution of NaHCO3, brine, dried (Na2SO4) and concentrated to provide the title compound.

Provenance & Evidence