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]-6-(4-fluoro-2-methoxyphenyl)-1-{[3-(methoxymethyl)-1,2,4-oxadiazol-5-yl]methyl}thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione

HRID 1476554Notes

Reaction equation

HRID 1476554 reaction equation
Cl.[F:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[S:17][C:16]3[C:15](=[O:18])[N:14]([CH:19]4[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]4)[C:13](=[O:25])[N:12]([CH2:26][C:27]4[O:31][N:30]=[C:29]([CH2:32][O:33][CH3:34])[N:28]=4)[C:11]=3[CH:10]=2)=[C:5]([O:35][CH3:36])[CH:4]=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:60]=[CH:59][C:55]([C:56](O)=[O:57])=[CH:54][CH:53]=3)=[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>[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]=[CH:54][C:55]([C:56]([N:22]4[CH2:23][CH2:24][CH:19]([N:14]5[C:15](=[O:18])[C:16]6[S:17][C:9]([C:6]7[CH:7]=[CH:8][C:3]([F:2])=[CH:4][C:5]=7[O:35][CH3:36])=[CH:10][C:11]=6[N:12]([CH2:26][C:27]6[O:31][N:30]=[C:29]([CH2:32][O:33][CH3:34])[N:28]=6)[C:13]5=[O:25])[CH2:20][CH2:21]4)=[O:57])=[CH:59][CH:60]=3)=[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]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 672589606-(4-fluoro-2-methoxyphenyl)-1-{[3-(methoxymethyl)-1,2,4-oxadiazol-5-yl]methyl}-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 672616163-[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]-6-(4-fluoro-2-methoxyphenyl)-1-{[3-(methoxymethyl)-1,2,4-oxadiazol-5-yl]methyl}thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

6-(4-fluoro-2-methoxyphenyl)-1-{[3-(methoxymethyl)-1,2,4-oxadiazol-5-yl]methyl}-3-(piperidin-4-yl)thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione hydrochloride (415 mg; compound B84) 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 (383 mg; compound C10) and HBTU (322 mg) in DCM (10 ml) in the presence of DIPEA (498 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, 100/0/to 0/100 (v/v)] and by preparative HPLC as a solid.

Sources & evidence

ORD record
ord-df29506c6d9342ec85db0b74f7d74b15
Source dataset
uspto-grants-2015_04
Patent number
US09018175B2

Reaction notes

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