Ethyl Acetate → (S)-tert-butyl 3-(3-carbamoyl-6-phenylpyrrolo[1,2-b]pyridazin-4-ylamino)piperidine-1-carboxylate

Participants

Role	Name	HCID	Charge
Reactant	Ethyl Acetate	HCID 8857	—
Reactant	Potassium Phosphate, Tribasic	HCID 62657	—
Reactant	Phenylboronic Acid	HCID 66827	—
Reactant	(S)-tert-butyl 3-(6-bromo-3-carbamoylpyrrolo[1,2-b]pyridazin-4-ylamino)piperidine-1-carboxylate	HCID 68291502	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	Dimethylformamide	HCID 6228	—
Product	(S)-tert-butyl 3-(3-carbamoyl-6-phenylpyrrolo[1,2-b]pyridazin-4-ylamino)piperidine-1-carboxylate	HCID 68291570	85.1%

Reaction Conditions

Temperature	130 °C

Reaction Steps

A solution of (S)-tert-butyl 3-(6-bromo-3-carbamoylpyrrolo[1,2-b]pyridazin-4-ylamino)piperidine-1-carboxylate (75 mg, 0.17 mmol), phenylboronic acid (31.3 mg, 0.26 mmol), and PdCl2(dppf) 6.3 mg, (0.009 mmol) in DMF (1.5 mL) was added aq. K3PO4 (2M, 0.26 mL) then heated at 130° C. for 25 min. The mixture was poured into ethyl acetate (with 20% heptane) and washed with water then sat. aq. NaHCO3. The organic layer was dried over Na2SO4, filtered and concentrated. The crude product was purified via column chromatography (50-75% ethyl acetate in heptane) to afford the title compound (63 mg, 85% yield). LCMS 436.16 (M+H)+; HPLC (conditions L): retention time=4.02 min.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08987268B2
Source dataset	uspto-grants-2015_03
ORD ID	ord-0e2edb18cfec491eaf24570dc83d7091
Source note	uspto-grants-2015_03