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HuagongsheHuagongshe Chemistry Print Report · For research reference only
HRID 2195495Generated: October 30, 2026

Morpholine → 4-(5-(2-Fluoro-4-nitrophenoxy)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-6-yl)morpholine

https://huagongshe.com/reaction/2195495

Reaction equation

Participants

RoleNameHCIDCharge
ReactantMorpholineHCID 8083—
ReactantPotassium HydroxideHCID 14797—
Reactant2-(Di-tert-butylphosphino)-2'-methyl-1,1'-biphenylHCID 2734937—
Reactant6-Bromo-5-(2-fluoro-4-nitrophenoxy)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazoleHCID 66766903—
CatalystBis(dibenzylideneacetone)palladiumHCID 9811564—
SolventWaterHCID 962—
Solventtert-ButanolHCID 6386—
SolventEthyl AcetateHCID 8857—
Product4-(5-(2-Fluoro-4-nitrophenoxy)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-6-yl)morpholineHCID 6676714656.5%

Reaction Conditions

Temperature70 °C

Reaction Steps

To a solution of 6-bromo-5-(2-fluoro-4-nitro-phenoxy)-1-(tetrahydropyran-2-yl)-1 H-indazole (8.0 g, 18 mmol) in tert-butanol (150 mL) and H2O (3.2 mL) is added Pd2(dba)3 (320 mg, 0.35 mmol), 2-di-tert-butylphosphino-2′-methylbiphenyl (480 mg, 1.54 mmol), KOH (3.2 g, 57 mmol) and morpholine (3.2 g, 36.7 mmol) under N2. After the mixture is stirred at 70° C. for 2 hours under a N2 atmosphere, it is filtered and the filtrate is concentrated. The residue is partitioned with EtOAc (100 mL) and saturated aqueous NH4Cl (30 mL). The organic layer is separated, dried over MgSO4, and concentrated. The residue is purified by silica gel column chromatography eluting with PE:EtOAc (3:1) to give the product (4.5 g, 56.5% yield). MS (m/z): 443.1 (M+H).

Provenance & Evidence

DOI10.6084/m9.figshare.5104873.v1
Patent numberUSRE043878E1
Source datasetuspto-grants-2012_12
ORD IDord-08353c5945734795af231fcbbb324da2
Source noteuspto-grants-2012_12