Acetamidine → 12-chloro-4-[3-methyl-1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6,13-triazatricyclo[8.4.0.02,6]tetra-deca1(14),2,4,10,12-pentaene

Participants

Role	Name	HCID	Charge
Reactant	Acetamidine	HCID 67171	—
Reactant	1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)	HCID 636044	—
Reactant	9-Chloro-2-iodo-5,6-dihydroimidazo[1,2-d]pyrido[3,4-f][1,4]oxazepine	HCID 58204780	—
Reactant	(2-Methoxypropyl)hydrazine	HCID 86671471	—
Catalyst	palladium(II) acetate	HCID 167845	—
Solvent	Acetic Acid	HCID 176	—
Solvent	Dimethylformamide	HCID 6228	—
Product	12-chloro-4-[3-methyl-1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6,13-triazatricyclo[8.4.0.02,6]tetra-deca1(14),2,4,10,12-pentaene	HCID 88932553	338.4%

Reaction Conditions

Temperature	40 °C

Reaction Steps

To a solution of 12-chloro-4-iodo-9-oxa-3,6,13-triazatricyclo[8.4.0.02,6]tetradeca-1(14),2,4,10,12-pentaene (2.0 g, 5.8 mmol) in dry DMF (20 mL) was added hydrochloric acetimidamide (595 mg, 6.30 mmol), Pd(OAc)2 (130 mg, 0.580 mmol), and Xantphos (695 mg, 1.2 mmol). The mixture was stirred at 40° C. for 3 h under carbon monoxide atmosphere. LCMS indicated complete conversion. Acetic acid (40 mL) and hydrochloric (2-methoxypropyl)hydrazine (1.3 g, 12 mmol) were added. The resultant mixture was stirred at 100° C. for 1 h. After concentration, the residue was purified by silica gel chromatography eluting with DCM/methanol (100:1) to give 12-chloro-4-[3-methyl-1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6,13-triazatricyclo[8.4.0.02,6]tetra-deca1(14),2,4,10,12-pentaene (1.4 g, 71% yield) as a white solid. LCMS (ESI) m/z: 345.3 [M+H+].

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09090628B2
Source dataset	uspto-grants-2015_07
ORD ID	ord-e965352863c84ee1af302f1cca37ae5e
Source note	uspto-grants-2015_07