Triphenylphosphine → 2-(5-Amino-1-{3-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-phenyl}-1H-pyrazol-3-yl)-2-methyl-propionitrile

To an ice cooled solution of Intermediate 20b (363 mg, 1.50 mmol), 2-(tetrahydro-2H-pyran-2-yloxy)ethanol (329 mg, 305 μL, 2.25 mmol) and triphenylphosphine (786 mg, 3.00 mmol) in anhydrous THF (10 mL) was added dropwise diisopropyl azodicarboxylate (606 mg, 590 μL), and the ice bath removed and stirring continued under an Ar atmosphere. After 3 h, a further 1.0 eq of diisopropyl azodicarboxylate was added and the reaction stirred overnight. The reaction mixture was then concentrated in vacuo and subjected to FCC, eluting with 5-50% EtOAc in cyclohexane. The isolated product was repurified using FCC, eluting with 2.5-7.5% Et2O in DCM, to afford the title compound as a yellow oil (317 mg, 57%). LCMS (Method 3): Rt 3.67 min, m/z 393.3 [M+Na].

1. customthe ice bath removed
2. stirringthe reaction stirred overnight
3. concentrationThe reaction mixture was then concentrated in vacuo
4. washeluting with 5-50% EtOAc in cyclohexane
5. customThe isolated product was repurified
6. washeluting with 2.5-7.5% Et2O in DCM

ORD-Eintrag

ord-31d7a239deb448f9aa8ef7bd59a146b6

Quelldatensatz

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09359354B2