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-[(2-ethyl-2H-tetrazol-5-yl)methyl]-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione

HRID 1476527Notes

Reaction equation

HRID 1476527 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]([OH:22])=O)=[CH:18][CH:17]=3)=[N:9][C@@H:8]3[CH2:25][CH2:26][S:27][CH2:28][C@@H:7]3[C:6]=2[CH:5]=1)[CH3:2].CCN(C(C)C)C(C)C.[CH2:38]([N:40]1[N:44]=[N:43][C:42]([CH2:45][N:46]2[C:51]3[CH:52]=[C:53]([C:55]4[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=4)[S:54][C:50]=3[C:49](=[O:61])[N:48]([CH:62]3[CH2:67][CH2:66][NH:65][CH2:64][CH2:63]3)[C:47]2=[O:68])=[N:41]1)[CH3:39]>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:65]4[CH2:66][CH2:67][CH:62]([N:48]5[C:49](=[O:61])[C:50]6[S:54][C:53]([C:55]7[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=7)=[CH:52][C:51]=6[N:46]([CH2:45][C:42]6[N:43]=[N:44][N:40]([CH2:38][CH3:39])[N:41]=6)[C:47]5=[O:68])[CH2:63][CH2:64]4)=[O:22])=[CH:23][CH:24]=3)=[N:9][C@@H:8]3[CH2:25][CH2:26][S:27][CH2:28][C@@H:7]3[C:6]=2[CH:5]=1)[CH3:2]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 672587131-[(2-ethyl-2H-tetrazol-5-yl)methyl]-6-phenyl-3-(piperidin-4-yl)thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione2×HCID 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 532354993-[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-[(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

To 4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]benzoic acid (160 mg; compound C10) dissolved in DCM (20 ml) HBTU (167 mg) and DIPEA (0.21 ml) are added and the reaction mixture is stirred for 30 min at RT. Subsequently, 1-[(2-ethyl-2H-tetrazol-5-yl)methyl]-6-phenyl-3-(piperidin-4-yl)thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione (175 mg; compound B39) is added and the reaction mixture is stirred for 24 h at RT. After extraction with a saturated solution of sodium hydrogen carbonate and a saturated solution of sodium chloride the organic phase is separated and dried over Na2SO4. After filtration the solvent is removed under reduced pressure to give the crude title product. After purification by flash column chromatography (silica gel, eluent: EtOAc) the title compound is obtained as a solid.

Workup

  1. stirringthe reaction mixture is stirred for 24 h at RT
  2. extractionAfter extraction with a saturated solution of sodium hydrogen carbonate
  3. customa saturated solution of sodium chloride the organic phase is separated
  4. dry with materialdried over Na2SO4
  5. filtrationAfter filtration the solvent
  6. customis removed under reduced pressure

Sources & evidence

ORD record
ord-9555484c3a5b416da47d576095bab4ab
Source dataset
uspto-grants-2015_04
Patent number
US09018175B2

Reaction notes

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