Cesium carbonate → 1-(2,6-Dichloro-3,5-dimethoxy-phenyl)-3-[6-(4-dimethylaminomethyl-2-nitro phenylamino)-pyrimidin-4-yl]-3-methyl-1-(2-trimethylsilanyl-ethoxymethyl)-urea

Participants

Role	Name	HCID	Charge
Reactant	Cesium carbonate	HCID 10796	—
Reactant	1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)	HCID 636044	—
Reactant	4-[(Dimethylamino)methyl]-2-nitroaniline	HCID 62183213	—
Reactant	1-(6-Chloropyrimidin-4-yl)-3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methyl-3-((2-(trimethylsilyl)ethoxy)methyl)urea	HCID 131736969	—
Catalyst	Bis(dibenzylideneacetone)palladium	HCID 9811564	—
Solvent	Methanol	HCID 887	—
Solvent	Toluene	HCID 1140	—
Product	1-(2,6-Dichloro-3,5-dimethoxy-phenyl)-3-[6-(4-dimethylaminomethyl-2-nitro phenylamino)-pyrimidin-4-yl]-3-methyl-1-(2-trimethylsilanyl-ethoxymethyl)-urea	HCID 131736972	30%

Reaction Conditions

Temperature	100 °C

Reaction Steps

To a stirred solution of 1-(6-chloro-pyrimidin-4-yl)-3-(2,6-dichloro-3,5-dimethoxy-phenyl)-1-methyl-3-(2-trimethylsilanyl-ethoxymethyl)-urea (procedure L, step b; 260 g, 0.5 mmol) in toluene (5 mL) was added 4-dimethylaminomethyl-2-nitro-phenylamine (100 g, 0.5 mmol), Cs2CO3 (400 g, 1.25 mmol), Pd2(dba)3 (46 g, 0.05 mmol), xantphos (90 g, 0.15 mmol). The solution was stirred at 100° C. overnight. LCMS showed major product peak. The solution was evaporated with silica gel and purified by flash chromatography on silica eluting with EtOAc (w(/0.5% TEA):MeOH (w/0.5% TEA)=10-10:0.5 to afford the desired product (100 mg, yield: 30%). MS (ESI): 680 [M+H]+.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09434697B2
Source dataset	uspto-grants-2016_09
ORD ID	ord-96636bab598d48a1a64d5edaac0f10f2
Source note	uspto-grants-2016_09