Tetrahydrofuran → N~2~-{2-Chloro-4-[(4-Methylpiperazin-1-Yl)carbonyl]phenyl}-N~2~,N~8~-Dimethyl-4,5-Dihydrothieno[3,2-D][1]benzoxepine-2,8-Dicarboxamide

Participants

Role	Name	HCID	Charge
Reactant	Tetrahydrofuran	HCID 8028	—
Reactant	1,8-Diazabicyclo(5.4.0)undec-7-ene	HCID 81184	—
Reactant	8-bromo-N-(2-chloro-4-(4-methylpiperazine-1-carbonyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide	HCID 56834369	—
Catalyst	Molybdenum carbonyl (Mo(CO)6)	HCID 98885	—
Catalyst	trans-Bis(acetato)bis[2-[bis(2-methylphenyl)phosphino]benzyl]dipalladium(II)	HCID 11104995	—
Solvent	Methylamine	HCID 6329	—
Solvent	Ethyl Acetate	HCID 8857	—
Product	N~2~-{2-Chloro-4-[(4-Methylpiperazin-1-Yl)carbonyl]phenyl}-N~2~,N~8~-Dimethyl-4,5-Dihydrothieno[3,2-D][1]benzoxepine-2,8-Dicarboxamide	HCID 44242776	32%

Reaction Conditions

Temperature	150 °C

Reaction Steps

To a solution containing 8-bromo-N-(2-chloro-4-(4-methylpiperazine-1-carbonyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide (0.075 g, 0.13 mmol) in tetrahydrofuran (1.50 mL, 18.5 mmol), 2.00 M of methylamine in tetrahydrofuran (0.196 mL) was added molybdenumhexacarbonyl (34.4 mg, 0.130 mmol), trans-di(mu-acetato)bis[o-(di-o-tolylphosphino)benzyl]dipalladium (II) (18.3 mg, 0.0196 mmol) then 1,8-diazabicyclo[5.4.0]undec-7-ene (9.75 uL, 0.0652 mmol) and capped quickly to prevent CO gas from escaping. The reaction mixture was heated in a microwave at 150° C. for 20 min. The reaction mixture was diluted with EtOAc then filtered thru celite. The combined organics were dried (Na2SO4), filtered and concentrated. The crude was submitted for RP HPLC to give 181 (yield 32%). MS: (ESI+) 553.2

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09309265B2
Source dataset	uspto-grants-2016_04
ORD ID	ord-33a6087e08a14cf8a7d2737c00c2fd57
Source note	uspto-grants-2016_04