Phosphorus oxychloride → 6-Chloro-8-[5-(1-cyclobutyl piperidin-4-ylmethyl)-[1,3,4]oxadiazol-2-yl]chroman-5-yl amine
반응식
[CH:1]1([N:5]2[CH2:10][CH2:9][CH:8]([CH2:11][C:12]([OH:14])=O)[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.P(Cl)(Cl)(Cl)=O.[NH2:20][C:21]1[C:30]([Cl:31])=[CH:29][C:28]([C:32]([NH:34][NH2:35])=O)=[C:27]2[C:22]=1[CH2:23][CH2:24][CH2:25][O:26]2>>[Cl:31][C:30]1[C:21]([NH2:20])=[C:22]2[C:27](=[C:28]([C:32]3[O:14][C:12]([CH2:11][CH:8]4[CH2:7][CH2:6][N:5]([CH:1]5[CH2:2][CH2:3][CH2:4]5)[CH2:10][CH2:9]4)=[N:35][N:34]=3)[CH:29]=1)[O:26][CH2:25][CH2:24][CH2:23]2참가 물질
실험 절차
To the (1-cyclobutyl piperidin-4-yl) acetic acid (725 mg, 3.52 mmol, obtained in preparation 4) was added phosphoryl chloride (4 mL). The mixture was stirred for 15 minutes and 5-Amino-6-chloro-chroman-8-carboxylic acid hydrazide (500 mg, 2.0 mmol) was added. The reaction mixture was gradually heated to reflux for 30 minutes. The reaction mixture was cooled to room temperature, triturated with hexanes (2×20 mL) and the crude mass was basified with aqueous sodium bicarbonate solution. The basified mixture was extracted with 10% methanol in dichloromethane. The organic layer was dried over anhydrous sodium sulphate and the solvent was removed under reduced pressure and was purified by silica gel column to obtain 6-chloro-8-[5-(1-cyclobutyl piperidin-4-ylmethyl)-[1,3,4]oxadiazol-2-yl]chroman-5-yl amine (250 mg). Yield: 30%.
후처리
- temperatureThe reaction mixture was gradually heated
- temperatureto reflux for 30 minutes
- customtriturated with hexanes (2×20 mL)
- extractionThe basified mixture was extracted with 10% methanol in dichloromethane
- dry with materialThe organic layer was dried over anhydrous sodium sulphate
- customthe solvent was removed under reduced pressure
- customwas purified by silica gel column
출처 및 근거
- ORD 기록
- ord-9b2f9f5c2a4642a8908024039ba696b3
- 출처 데이터셋
- uspto-grants-2015_07
- 특허 번호
- US09079894B2
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