Formaldehyde → HCID 14457551、化合物

反応式

[CH:1]1[CH:6]=[CH:5][C:4]([CH2:7][N:8]2[CH:12]=[N:11][C:10]([CH2:13][C@H](N)C(O)=O)=[CH:9]2)=[CH:3][CH:2]=1.[CH2:19]=[O:20].S(Cl)(Cl)=O.[OH2:25]>>[CH3:19][O:20][C:9]([CH:10]1[NH:11][CH2:13][C:10]2[N:11]=[CH:12][N:8]([CH2:7][C:4]3[CH:3]=[CH:2][CH:1]=[CH:6][CH:5]=3)[C:9]=2[CH2:13]1)=[O:25]

参加物

反応物 4

HCID 712Formaldehyde

HCID 962Water

HCID 24386Thionyl Chloride

HCID 193138Poly(1-benzylhistidine)

生成物 1

HCID 14457551HCID 14457551、化合物収率 71%

反応条件

温度: 0 °C

実験手順

A solution of H-His-(Bzl)-OH (2.0 g, 8.16 mmol) and formaldehyde (37% in water, 0.92 ml, 12.24 mmol) in water (16 ml) was heated to reflux for 4 hours and concentrated to dryness. The residue was dissolved in methanol (4.6 ml) cooled to 0° C. and treated with thionyl chloride (0.6 ml, 8.12 mmol). The reaction mixture was reflux for 2.5 hours and concentrated. The solid was dissolved in dichloromethane, washed with a saturated solution of sodium hydrogenocarbonate, brine, dried over sodium sulfate and concentrated to dryness to yield 1-Benzyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid methyl ester (1.58 g, 71%). The ester was dissolved in tetrahydrofuran (26 ml), cooled to 0° C. and treated with 2,3-Dichloro-5,6-dicyanobenzoquinone (2.9 g, 12.81 mmol) in tetrahydrofuran (26 ml) and the reaction mixture was reflux for 4 hours. The solvent was removed and the black residue was dissolved in dichloromethane and treated with a 1M aqueous solution of sodium hydroxide. The aqueous solution was extracted several times with dichloromethane. The combined organic extracts were washed with brine, dried over sodium sulfate, concentrated and purified by flash chromatography over silica gel (gradient ethyl acetate/methanol: 0-10%) to yield 1-Benzyl-1H-imidazo[4,5-c]pyridin-6-carboxylic acid methyl ester (525 mg, 34%) as a beige solid.