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-(methoxymethyl)-1,3,4-oxadiazol-2-yl]methyl)-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione

HRID 1476521Notes

Reaction equation

HRID 1476521 reaction equation
Cl.[CH3:2][O:3][CH2:4][C:5]1[O:9][C:8]([CH2:10][N:11]2[C:16]3[CH:17]=[C:18]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[S:19][C:15]=3[C:14](=[O:26])[N:13]([CH:27]3[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]3)[C:12]2=[O:33])=[N:7][N:6]=1.[CH2:34]([O:36][C:37]1[C:46]([O:47][CH3:48])=[CH:45][C:44]2[C:43]([C:49]3[CH:57]=[CH:56][C:52]([C:53](O)=[O:54])=[CH:51][CH:50]=3)=[N:42][C@@H:41]3[CH2:58][CH2:59][S:60][CH2:61][C@@H:40]3[C:39]=2[CH:38]=1)[CH3:35].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH2:34]([O:36][C:37]1[C:46]([O:47][CH3:48])=[CH:45][C:44]2[C:43]([C:49]3[CH:50]=[CH:51][C:52]([C:53]([N:30]4[CH2:31][CH2:32][CH:27]([N:13]5[C:14](=[O:26])[C:15]6[S:19][C:18]([C:20]7[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=7)=[CH:17][C:16]=6[N:11]([CH2:10][C:8]6[O:9][C:5]([CH2:4][O:3][CH3:2])=[N:6][N:7]=6)[C:12]5=[O:33])[CH2:28][CH2:29]4)=[O:54])=[CH:56][CH:57]=3)=[N:42][C@@H:41]3[CH2:58][CH2:59][S:60][CH2:61][C@@H:40]3[C:39]=2[CH:38]=1)[CH3:35]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 672585721-{[5-(methoxymethyl)-1,3,4-oxadiazol-2-yl]methyl}-6-phenyl-3-(piperidin-4-yl)thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione hydrochlorideHCID 672590924-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]benzoic acid

Product 1

HCID 532465063-[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-(methoxymethyl)-1,3,4-oxadiazol-2-yl]methyl)-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1-{[5-(methoxymethyl)-1,3,4-oxadiazol-2-yl]methyl}-6-phenyl-3-(piperidin-4-yl)thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione hydrochloride (250 mg; compound B33) 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 (223 mg; compound C10) and HBTU (232 mg) in DCM (15 ml) in the presence of DIPEA (0.36 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.

Sources & evidence

ORD record
ord-e16ad18e57684ad3a5ce45abb15a7678
Source dataset
uspto-grants-2015_04
Patent number
US09018175B2

Reaction notes

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