Participants
| Role | Name | HCID | Charge |
|---|
| Reactant | Sodium Hydroxide | HCID 14798 | — |
| Reactant | Ethyl 4-piperidinecarboxylate | HCID 70770 | — |
| Reactant | Diisopropylethylamine | HCID 81531 | — |
| Reactant | Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) | HCID 2733084 | — |
| Reactant | 3-((4-Oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoic acid | HCID 25131906 | — |
| Solvent | Water | HCID 962 | — |
| Solvent | Tetrahydrofuran | HCID 8028 | — |
| Solvent | Dimethylacetamide | HCID 31374 | — |
| Product | HCID 59833507 | HCID 59833507 | 65% |
Reaction Steps
3-(4-Oxo-3,4-dihydrophthalazin-1-ylmethyl)benzoic acid (A) (7.0 g, 0.25 mol), ethyl isonipecotate (5 ml, 0.32 mol), 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) (12.3 g, 0.32 mol) and N,N,-diisopropylethylamine (10.0 ml, 0.55 mol) were added to dimethylacetamide (40 ml) and stirred for 18 h. Water (100 ml) was added to the reaction mixture and the product was extracted into dichloromethane (4×50 ml). The combined organic layers were washed with water (3×100 ml), dried over MgSO4, filtered and evaporated in vacuo to yield an oil. To a solution of the oil in tetrahydrofuran (100 ml) was added 10% aqueous sodium hydroxide solution (20 ml) and the reaction was stirred for 18 hours. The reaction was concentrated, washed with ethyl acetate (2×30 ml) and acidified with 2M HCl to pH 2. The aqueous layer was extracted with dichloromethane (2×100 ml), then the extracts were dried over MgSO4, filtered and evaporated to yield 1-[3-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)benzoyl]piperidine-4-carboxylic acid (C) as a yellow solid (7.0 g, 65%), m/z [M+1]+ 392 (96% purity), δH 1.3-1.8 (5H, m), 2.8-3.1 (4H, m), 4.4 (2H, s), 7.2-7.3 (1H, m), 7.3-7.4 (1H, m), 7.7-8.0 (5H, m), 8.2-8.3 (1H, m), 12.6 (1H, s).
Provenance & Evidence
| DOI | 10.6084/m9.figshare.5104873.v1 |
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| Patent number | US07981889B2 |
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| Source dataset | uspto-grants-2011_07 |
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| ORD ID | ord-265a2ee2c1b545fcb71de82170cf5336 |
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| Source note | uspto-grants-2011_07 |
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