Diisopropylethylamine → 6-(2,5-dimethoxyphenyl)-3-[1-({3-[(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-[(2-ethyl-2H-tetrazol-5-yl)methyl]thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione

HRID 1476548Notes

Reaction equation

HRID 1476548 reaction equation
Cl.[CH3:2][O:3][C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[CH:6][C:5]=1[C:12]1[S:20][C:19]2[C:18](=[O:21])[N:17]([CH:22]3[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]3)[C:16](=[O:28])[N:15]([CH2:29][C:30]3[N:31]=[N:32][N:33]([CH2:35][CH3:36])[N:34]=3)[C:14]=2[CH:13]=1.[CH2:37]([O:39][C:40]1[C:49]([O:50][CH3:51])=[CH:48][C:47]2[C:46]([C:52]3[CH:53]=[C:54]([CH:58]=[CH:59][CH:60]=3)[C:55](O)=[O:56])=[N:45][C@@H:44]3[CH2:61][CH2:62][S:63][CH2:64][C@@H:43]3[C:42]=2[CH:41]=1)[CH3:38].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>[CH3:2][O:3][C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[CH:6][C:5]=1[C:12]1[S:20][C:19]2[C:18](=[O:21])[N:17]([CH:22]3[CH2:27][CH2:26][N:25]([C:55]([C:54]4[CH:58]=[CH:59][CH:60]=[C:52]([C:46]5[C:47]6[CH:48]=[C:49]([O:50][CH3:51])[C:40]([O:39][CH2:37][CH3:38])=[CH:41][C:42]=6[C@H:43]6[CH2:64][S:63][CH2:62][CH2:61][C@H:44]6[N:45]=5)[CH:53]=4)=[O:56])[CH2:24][CH2:23]3)[C:16](=[O:28])[N:15]([CH2:29][C:30]3[N:31]=[N:32][N:33]([CH2:35][CH3:36])[N:34]=3)[C:14]=2[CH:13]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 672584146-(2,5-dimethoxyphenyl)-1-[(2-ethyl-2H-tetrazol-5-yl)methyl]-3-(piperidin-4-yl)thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione hydrochlorideHCID 672606663-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]benzoic acid2×

Product 1

HCID 672593826-(2,5-dimethoxyphenyl)-3-[1-({3-[(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-[(2-ethyl-2H-tetrazol-5-yl)methyl]thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

6-(2,5-dimethoxyphenyl)-1-[(2-ethyl-2H-tetrazol-5-yl)methyl]-3-(piperidin-4-yl)thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione hydrochloride (137 mg; compound B80) is reacted with 3-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]benzoic acid (102 mg; compound C8) and HBTU (213 mg) in DCM (10 ml) in the presence of DIPEA (264 mg) according to the procedure described in example 2 to afford the title compound after purification by flash column chromatography [amino phase silica gel, eluation gradient: Cyclohexane/EtOAc/DCM, 100/0/0 to 50/40/10 to 30/60/10 to 0/90/10 (v/v/v)] and preparative HPLC as a solid.

Sources & evidence

ORD record
ord-e642319895024229b92ae48259a3f7ff
Source dataset
uspto-grants-2015_04
Patent number
US09018175B2

Reaction notes

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