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

HRID 1476561Notes

Reaction equation

HRID 1476561 reaction equation
Cl.[CH3:2][N:3]1[CH:7]=[N:6][C:5]([CH2:8][N:9]2[C:14]3[CH:15]=[C:16]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[S:17][C:13]=3[C:12](=[O:24])[N:11]([CH:25]3[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]3)[C:10]2=[O:31])=[N:4]1.[CH2:32]([O:34][C:35]1[C:44]([O:45][CH3:46])=[CH:43][C:42]2[C:41]([C:47]3[CH:55]=[CH:54][C:50]([C:51](O)=[O:52])=[CH:49][CH:48]=3)=[N:40][C@@H:39]3[CH2:56][CH2:57][S:58][CH2:59][C@@H:38]3[C:37]=2[CH:36]=1)[CH3:33].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.S(=O)(=O)(O)[O-].[K+]>C(Cl)Cl>[CH2:32]([O:34][C:35]1[C:44]([O:45][CH3:46])=[CH:43][C:42]2[C:41]([C:47]3[CH:48]=[CH:49][C:50]([C:51]([N:28]4[CH2:29][CH2:30][CH:25]([N:11]5[C:12](=[O:24])[C:13]6[S:17][C:16]([C:18]7[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=7)=[CH:15][C:14]=6[N:9]([CH2:8][C:5]6[N:6]=[CH:7][N:3]([CH3:2])[N:4]=6)[C:10]5=[O:31])[CH2:26][CH2:27]4)=[O:52])=[CH:54][CH:55]=3)=[N:40][C@@H:39]3[CH2:56][CH2:57][S:58][CH2:59][C@@H:38]3[C:37]=2[CH:36]=1)[CH3:33]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 516920Potassium bisulfateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67258926HCID 67258926, compoundHCID 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 672582453-[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-[(1-methyl-1H-1,2,4-triazol-3-yl)methyl]-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 1-[(1-methyl-1H-1,2,4-triazol-3-yl)methyl]-6-phenyl-3-(piperidin-4-yl)thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione hydrochloride (249 mg, compound B92), 4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]benzoic acid (210 mg; compound C10) and HATU (267 mg) in DCM (7.0 ml) is added DIPEA (0.28 ml). The reaction mixture is stirred at RT for 14 h. Aqueous potassium bisulfate solution (10% w/w, 10 ml) is added and the mixture is extracted with DCM. After filtration using a phase separator the organic layer is concentrated under reduced pressure and the residue is purified by preparative HPLC to yield the title compound as a solid.

Workup

  1. extractionthe mixture is extracted with DCM
  2. filtrationAfter filtration
  3. concentrationis concentrated under reduced pressure
  4. customthe residue is purified by preparative HPLC

Sources & evidence

ORD record
ord-59b57d76a6e64f0abee05170f02bc8d1
Source dataset
uspto-grants-2015_04
Patent number
US09018175B2

Reaction notes

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