関与物質
| 役割 | 名称 | HCID | 仕込み量 |
|---|
| 反応物 | Diisopropylethylamine | HCID 81531 | — |
| 反応物 | O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate | HCID 2733207 | — |
| 反応物 | 4-Piperidinecarboxylic acid, 1-methyl-, hydrochloride (1:1) | HCID 2760043 | — |
| 反応物 | Dichloromethane methanol ammonium hydroxide | HCID 21896990 | — |
| 反応物 | HCID 68649268 | HCID 68649268 | — |
| 溶媒 | Dichloromethane | HCID 6344 | — |
| 溶媒 | Ethyl acetate hexane | HCID 21226206 | — |
| 生成物 | HCID 178480346 | HCID 178480346 | 69.3% |
反応手順
Ethyl 3-[(4-fluorobenzoyl)amino]-6,6-dimethyl-5,6-dihydropyrrolo[3,4-c]pyrazole-1(4H)-carboxylate hydrochloride (0.5 g, 1.3 mmol), in dichloromethane (25 ml), was treated with N,N-diisopropylethylamine (1.13 ml, 6.5 mmol, 5 eq) and TBTU (0.542 g, 1.69 mmol, 1.3 eq), at room temperature for 1 hour, and then 1-methyl-piperidine-4-carboxylic acid hydrochloride (0.29 g, 1.61 mmol, 1.2 eq) was added. The reaction was stirred overnight (TLC: CH2Cl2/MeOH 90/10). The solution was washed with saturated sodium hydrogencarbonate aqueous solution and brine, the organic phase was dried over sodium sulfate and concentrated. The residue was dissolved in methanol (16 ml), treated with TEA (2 ml, 14.3 mmol, 11 eq) and stirred overnight at room temperature. (TLC: CH2Cl2/MeOH/NH4OH 90/10/1). After evaporation, the solid was purified by flash chromatography (eluent: CH2Cl2/MeOH/NH4OH 90/10/2). The solid was treated with diisopropylether and filtered to afford 0.36 g of the title compound in 69% yield.
情報源と証拠
| DOI | 10.6084/m9.figshare.5104873.v1 |
|---|
| 特許番号 | US08481585B2 |
|---|
| 出典データセット | uspto-grants-2013_07 |
|---|
| ORD ID | ord-3963e645ccbc4f95ad959c0173a1757f |
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| 出典メモ | uspto-grants-2013_07 |
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