Formaldehyde → 4-Chloro-6,7,8,9-tetrahydro-5H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carboxylic acid methyl ester
反応式
[CH3:1][O:2][C:3](=[O:17])[CH:4]([NH2:16])[CH2:5][C:6]1[C:14]2[C:9](=[N:10][CH:11]=[CH:12][C:13]=2[Cl:15])[NH:8][CH:7]=1.[CH2:18]=O>N1C=CC=CC=1>[CH3:1][O:2][C:3]([CH:4]1[NH:16][CH2:18][C:7]2[NH:8][C:9]3[N:10]=[CH:11][CH:12]=[C:13]([Cl:15])[C:14]=3[C:6]=2[CH2:5]1)=[O:17]参加物
反応条件
- 温度
- 100 °C
実験手順
A suspension of 2-amino-3-(4-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-propionic acid methyl ester (3.5 g, 10 mmol) in pyridine (25 mL) was treated with formaldehyde solution (37% in water, 0.90 mL) and the resulting mixture was heated to 100° C. for 1.25 hours. The mixture was allowed to cool to ambient temperature then evaporated in-vacuo. The resultant residue was treated with saturated aqueous sodium carbonate solution (15 mL) and the resultant solid collected by filtration and washed with water (20 mL). The filtrate was extracted with 20% methanol in dichloromethane (6×25 mL). The combined organic phase was combined with solid and concentrated in-vacuo to afford the title compound as a brown residue (2.1 g, 87%). LCMS (Method B): RT=2.36 min, M+H+=266. 1H NMR (400 MHz, DMSO-d6): 11.66 (s, 1H), 8.02 (d, J=5.2 Hz, 1H), 7.06 (d, J=5.1 Hz, 1H), 4.01-3.71 (m, 3H), 3.69 (s, 3H), 3.19 (dd, J=15.4, 4.7 Hz, 1H), 2.94 (dd, J=15.4, 8.9 Hz, 1H).
後処理
- temperatureto cool to ambient temperature
- customthen evaporated in-vacuo
- additionThe resultant residue was treated with saturated aqueous sodium carbonate solution (15 mL)
- filtrationthe resultant solid collected by filtration
- washwashed with water (20 mL)
- extractionThe filtrate was extracted with 20% methanol in dichloromethane (6×25 mL)
- concentrationconcentrated in-vacuo
出典と根拠
- ORDレコード
- ord-589d6f0932ab428d9a2b17c92e51079c
- 出典データセット
- uspto-grants-2016_09
- 特許番号
- US09440976B2
反応ノート
読み込み中…