1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 6-(3,4-difluorophenyl)-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-[(3-ethyl-1,2,4-oxadiazol-5-yl)methyl]thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione

HRID 1476559Notes

Reaction equation

HRID 1476559 reaction equation
Cl.[F:2][C:3]1[CH:4]=[C:5]([C:10]2[S:18][C:17]3[C:16](=[O:19])[N:15]([CH:20]4[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]4)[C:14](=[O:26])[N:13]([CH2:27][C:28]4[O:32][N:31]=[C:30]([CH2:33][CH3:34])[N:29]=4)[C:12]=3[CH:11]=2)[CH:6]=[CH:7][C:8]=1[F:9].[CH2:35]([O:37][C:38]1[C:47]([O:48][CH3:49])=[CH:46][C:45]2[C:44]([C:50]3[CH:58]=[CH:57][C:53]([C:54](O)=[O:55])=[CH:52][CH:51]=3)=[N:43][C@@H:42]3[CH2:59][CH2:60][S:61][CH2:62][C@@H:41]3[C:40]=2[CH:39]=1)[CH3:36].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>CN(C=O)C>[F:2][C:3]1[CH:4]=[C:5]([C:10]2[S:18][C:17]3[C:16](=[O:19])[N:15]([CH:20]4[CH2:21][CH2:22][N:23]([C:54]([C:53]5[CH:57]=[CH:58][C:50]([C:44]6[C:45]7[CH:46]=[C:47]([O:48][CH3:49])[C:38]([O:37][CH2:35][CH3:36])=[CH:39][C:40]=7[C@H:41]7[CH2:62][S:61][CH2:60][CH2:59][C@H:42]7[N:43]=6)=[CH:51][CH:52]=5)=[O:55])[CH2:24][CH2:25]4)[C:14](=[O:26])[N:13]([CH2:27][C:28]4[O:32][N:31]=[C:30]([CH2:33][CH3:34])[N:29]=4)[C:12]=3[CH:11]=2)[CH:6]=[CH:7][C:8]=1[F:9]

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 672590924-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]benzoic acidHCID 709760686-(3,4-difluorophenyl)-1-[(3-ethyl-1,2,4-oxadiazol-5-yl)methyl]-3-(piperidin-4-yl)thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione hydrochloride2×

Product 1

HCID 708924446-(3,4-difluorophenyl)-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-[(3-ethyl-1,2,4-oxadiazol-5-yl)methyl]thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

6-(3,4-difluorophenyl)-1-[(3-ethyl-1,2,4-oxadiazol-5-yl)methyl]-3-(piperidin-4-yl)thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione hydrochloride (228 mg; compound B89) 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 (191 mg; compound C10) and HOBt (74 mg) and EDCI (92 mg) in DMF (10 ml) according to the procedure described in example 46 to afford the title compound after purification by flash column chromatography [amino phase silica gel, eluation gradient: DCM/ethanol, 100/0/to 95/5 (v/v)] and by preparative HPLC as a solid.

Sources & evidence

ORD record
ord-ef79a9d735424ba3940cd7370ad6a28a
Source dataset
uspto-grants-2015_04
Patent number
US09018175B2

Reaction notes

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