Diisopropylethylamine → 6-(1,3-benzodioxol-5-yl)-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]thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione

HRID 1476541Notes

Reaction equation

HRID 1476541 reaction equation
Cl.[O:2]1[C:6]2[CH:7]=[CH:8][C:9]([C:11]3[S:19][C:18]4[C:17](=[O:20])[N:16]([CH:21]5[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]5)[C:15](=[O:27])[N:14]([CH2:28][C:29]5[N:30]=[N:31][N:32]([CH2:34][CH3:35])[N:33]=5)[C:13]=4[CH:12]=3)=[CH:10][C:5]=2[O:4][CH2:3]1.[CH2:36]([O:38][C:39]1[C:48]([O:49][CH3:50])=[CH:47][C:46]2[C:45]([C:51]3[CH:59]=[CH:58][C:54]([C:55](O)=[O:56])=[CH:53][CH:52]=3)=[N:44][C@@H:43]3[CH2:60][CH2:61][S:62][CH2:63][C@@H:42]3[C:41]=2[CH:40]=1)[CH3:37].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.CN(C=O)C>[O:2]1[C:6]2[CH:7]=[CH:8][C:9]([C:11]3[S:19][C:18]4[C:17](=[O:20])[N:16]([CH:21]5[CH2:22][CH2:23][N:24]([C:55]([C:54]6[CH:58]=[CH:59][C:51]([C:45]7[C:46]8[CH:47]=[C:48]([O:49][CH3:50])[C:39]([O:38][CH2:36][CH3:37])=[CH:40][C:41]=8[C@H:42]8[CH2:63][S:62][CH2:61][CH2:60][C@H:43]8[N:44]=7)=[CH:52][CH:53]=6)=[O:56])[CH2:25][CH2:26]5)[C:15](=[O:27])[N:14]([CH2:28][C:29]5[N:30]=[N:31][N:32]([CH2:34][CH3:35])[N:33]=5)[C:13]=4[CH:12]=3)=[CH:10][C:5]=2[O:4][CH2:3]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 672590924-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]benzoic acidHCID 709762226-(1,3-benzodioxol-5-yl)-1-[(2-ethyl-2H-tetrazol-5-yl)methyl]-3-(piperidin-4-yl)thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione hydrochloride

Product 1

HCID 709762476-(1,3-benzodioxol-5-yl)-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]thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

6-(1,3-benzodioxol-5-yl)-1-[(2-ethyl-2H-tetrazol-5-yl)methyl]-3-(piperidin-4-yl)thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione hydrochloride (94 mg; compound B77) 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 (72 mg; compound C10) and HBTU (151 mg) in DCM/DMF (15 ml/1 ml) in the presence of DIPEA (188 mg) according to the procedure described in example 2 to afford the title compound after purification by two-time flash column chromatography [amino phase silica gel, eluation gradient: Cyclohexane/EtOAc/DCM, 100/0/0 to 65/30/5 to 30/60/10 to 0/90/10 (v/v/v)].

Sources & evidence

ORD record
ord-9018638ae60d42d2a27c08e3e4684af1
Source dataset
uspto-grants-2015_04
Patent number
US09018175B2

Reaction notes

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