Acetamidine → 12-bromo-4-[1-(2-methoxypropyl)-3-methyl-1H-1,2,4-triazol-5-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca1(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-Bromo-2-iodo-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine	HCID 58204858	—
Reactant	(2-Methoxypropyl)hydrazine	HCID 86671471	—
Catalyst	palladium(II) acetate	HCID 167845	—
Solvent	Acetic Acid	HCID 176	—
Solvent	Dimethylformamide	HCID 6228	—
Product	12-bromo-4-[1-(2-methoxypropyl)-3-methyl-1H-1,2,4-triazol-5-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca1(14),2,4,10,12-pentaene	HCID 68312993	325%

Reaction Conditions

Temperature	40 °C

Reaction Steps

To a solution of 12-bromo-4-iodo-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca1(14),2,4,10,12-pentaene (1.0 g, 2.6 mmol) in dry DMF (20 mL) was added hydrochloric acetimidamide (266 mg, 2.81 mmol), Pd(OAc)2 (58 mg, 0.26 mmol), and Xantphos (305 mg, 0.520 mmol). The reaction 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 (577 mg, 5.20 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-bromo-4-[1-(2-methoxypropyl)-3-methyl-1H-1,2,4-triazol-5-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca1(14),2,4,10,12-pentaene (707 mg, 65% yield) as white solid. LCMS (ESI) m/z: 418.3 [M+H+].

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09090628B2
Source dataset	uspto-grants-2015_07
ORD ID	ord-206ad0d57fff456c975f5a33409fc63a
Source note	uspto-grants-2015_07