Acetic Acid → 7-methoxy-3-methyl-4,5-dihydro-1H-pyrido[2,3-b][1,4]diazepin-2(3H)-one

HRID 1485462Notes

Reaction equation

C[O:2][C:3](=O)[CH:4]([CH3:18])[CH2:5][NH:6][C:7]1[C:12]([N+:13]([O-])=O)=[CH:11][CH:10]=[C:9]([O:16][CH3:17])[N:8]=1.C(O)(=O)C.C(=O)([O-])O.[Na+]>C(O)C.[Fe]>[CH3:17][O:16][C:9]1[CH:10]=[CH:11][C:12]2[NH:13][C:3](=[O:2])[CH:4]([CH3:18])[CH2:5][NH:6][C:7]=2[N:8]=1

Participants

Conditions

Temperature: 90 °C

Procedure

To a solution of methyl-3-((6-methoxy-3-nitropyridin-2-yl)amino)-2-methylpropanoate (4.0 g, 14.86 mmol) in anhydrous ethanol (50 mL) was added iron powder reduced (8.30 g, 148.56 mmol) and acetic acid (17.84 g, 297.12 mmol). The mixture was stirred at 90° C. for 12 hours. The reaction mixture was neutralized to pH 8 with solid sodium hydrogencarbonate, concentrated in vacuo and washed with water (20 mL), filtered. The filtrate was extracted with acetic ester (200 mL×3). The combined organic phase was dried by anhydrous sodium sulphate, and then filtered. The filtrate was concentrated and purified by column chromatograph silica gel (elute: dichloromethane/Methanol: 80:1→50:1) to give 7-methoxy-3-methyl-4,5-dihydro-1H-pyrido[2,3-b][1,4]diazepin-2(3H)-one (3 g, 96%) as a yellow solid.

Workup

concentrationconcentrated in vacuo
washwashed with water (20 mL)
filtrationfiltered
extractionThe filtrate was extracted with acetic ester (200 mL×3)
dry with materialThe combined organic phase was dried by anhydrous sodium sulphate
filtrationfiltered
concentrationThe filtrate was concentrated
custompurified by column chromatograph silica gel (elute: dichloromethane/Methanol: 80:1→50:1)

Sources & evidence

ORD record: ord-7db110505ca545778031aa150df915a3
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09422292B2

Reaction notes

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