Diisopropylethylamine → 3-[1-({4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]phenyl}carbonyl)piperidin-4-yl]-1-[(5-methylisoxazol-3-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-[(5-methylisoxazol-3-yl)methyl]-6-phenyl-3-(piperidin-4-yl)thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione hydrochloride	HCID 67258451	—
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]phenyl}carbonyl)piperidin-4-yl]-1-[(5-methylisoxazol-3-yl)methyl]-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione	HCID 53246390	—

Reaction Steps

1-[(5-methylisoxazol-3-yl)methyl]-6-phenyl-3-(piperidin-4-yl)thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione hydrochloride (250 mg; compound B31) 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 (238 mg; compound C10) and HBTU (246 mg) in DCM (15 ml) in the presence of DIPEA (0.38 ml) according to the procedure described in example 2 to afford the title compound after purification by flash column chromatography [silica gel, eluation gradient: DCM/MeOH, 1/0 to 3/2 (v/v)] and preparative HPLC as a solid.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09018175B2
Source dataset	uspto-grants-2015_04
ORD ID	ord-2f15b7e679d4478aa57e7f67269f8c7d
Source note	uspto-grants-2015_04