Diisopropylethylamine → 3-(1-{4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]benzoyl}piperidin-4-yl)-1-([3-(methoxymethyl)-1,2,4-oxadiazol-5-yl]methyl)-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 2733084	—
Reactant	1-{[3-(methoxymethyl)-1,2,4-oxadiazol-5-yl]methyl}-6-phenyl-3-piperidin-4-ylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione hydrochloride	HCID 67259064	—
Reactant	4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]benzoic acid	HCID 67259092	—
Solvent	Dichloromethane	HCID 6344	—
Product	3-(1-{4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]benzoyl}piperidin-4-yl)-1-([3-(methoxymethyl)-1,2,4-oxadiazol-5-yl]methyl)-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione	HCID 53246745	—

Reaction Steps

1-{[3-(methoxymethyl)-1,2,4-oxadiazol-5-yl]methyl}-6-phenyl-3-piperidin-4-ylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione hydrochloride (148 mg; compound B40) is reacted with 4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]benzoic acid (120 mg; compound C10) and HBTU (126 mg) in DCM (8 ml) in the presence of DIPEA (155 mg) according to the procedure described in example 2 to afford the title compound after purification by flash column chromatography [silica gel, eluation gradient: cyclohexane/EtOAc, 1/1.5 to 0/1 (v/v)] as a solid.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09018175B2
Source dataset	uspto-grants-2015_04
ORD ID	ord-1385f858de1b4e76a674d17b51565531
Source note	uspto-grants-2015_04