Diisopropylethylamine → 3-[1-({4-[(4aR,10bR)-9-ethoxy-8-methoxy-2,2-dioxido-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]-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione

HRID 1476532Notes

Reaction equation

HRID 1476532 reaction equation
[CH2:1]([O:3][C:4]1[C:13]([O:14][CH3:15])=[CH:12][C:11]2[C:10]([C:16]3[CH:24]=[CH:23][C:19]([C:20](O)=[O:21])=[CH:18][CH:17]=3)=[N:9][C@@H:8]3[CH2:25][CH2:26][S:27](=[O:30])(=[O:29])[CH2:28][C@@H:7]3[C:6]=2[CH:5]=1)[CH3:2].Cl.[CH2:32]([N:34]1[N:38]=[N:37][C:36]([CH2:39][N:40]2[C:45]3[CH:46]=[C:47]([C:49]4[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=4)[S:48][C:44]=3[C:43](=[O:55])[N:42]([CH:56]3[CH2:61][CH2:60][NH:59][CH2:58][CH2:57]3)[C:41]2=[O:62])=[N:35]1)[CH3:33].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>[CH2:1]([O:3][C:4]1[C:13]([O:14][CH3:15])=[CH:12][C:11]2[C:10]([C:16]3[CH:17]=[CH:18][C:19]([C:20]([N:59]4[CH2:60][CH2:61][CH:56]([N:42]5[C:43](=[O:55])[C:44]6[S:48][C:47]([C:49]7[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=7)=[CH:46][C:45]=6[N:40]([CH2:39][C:36]6[N:37]=[N:38][N:34]([CH2:32][CH3:33])[N:35]=6)[C:41]5=[O:62])[CH2:57][CH2:58]4)=[O:21])=[CH:23][CH:24]=3)=[N:9][C@@H:8]3[CH2:25][CH2:26][S:27](=[O:29])(=[O:30])[CH2:28][C@@H:7]3[C:6]=2[CH:5]=1)[CH3:2]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67258712HCID 67258712, compoundHCID 67259494HCID 67259494, compound2×

Product 1

HCID 532468683-[1-({4-[(4aR,10bR)-9-ethoxy-8-methoxy-2,2-dioxido-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]-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The title compound is prepared analogously as described for example 1 (however, stirring is performed for 12 h at RT) using 4-[(4aR,10bR)-9-ethoxy-8-methoxy-2,2-dioxido-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]benzoic acid (330 mg; compound C4), 1-[(2-ethyl-2H-tetrazol-5-yl)methyl]-6-phenyl-3-(piperidin-4-yl)thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione hydrochloride (365 mg; hydrochloride salt of compound B39), HBTU (322 mg), DIPEA (0.65 ml) and DCM (20 ml). The crude product is purified by flash column chromatography [silica gel, eluant: DCM/MeOH, 19/1 (v/v)] to yield the title compound as a solid.

Workup

  1. customThe title compound is prepared analogously
  2. customThe crude product is purified by flash column chromatography [silica gel, eluant: DCM/MeOH, 19/1 (v/v)]

Sources & evidence

ORD record
ord-d548005fde224e8ba785d3b6cf62a3cc
Source dataset
uspto-grants-2015_04
Patent number
US09018175B2

Reaction notes

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