Acetic Acid → tert-butyl 4-(3-acetyl-2-oxo-2H-pyrano[2,3-b]pyridin-7-yl)-1,4-diazepane-1-carboxylate

HRID 2206336Notes

Reaction equation

[CH:1]([C:3]1[CH:4]=[CH:5][C:6]([N:10]2[CH2:16][CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12][CH2:11]2)=[N:7][C:8]=1[OH:9])=O.N1CCCCC1.C(O)(=O)C.[C:34](OCC)(=[O:39])[CH2:35][C:36]([CH3:38])=[O:37]>CCO>[C:36]([C:35]1[C:34](=[O:39])[O:9][C:8]2=[N:7][C:6]([N:10]3[CH2:16][CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12][CH2:11]3)=[CH:5][CH:4]=[C:3]2[CH:1]=1)(=[O:37])[CH3:38]

Participants

Conditions

Temperature: 90 °C

Procedure

To a solution of tert-butyl 4-(5-formyl-6-hydroxypyridin-2-yl)-1,4-diazepane-1-carboxylate (600 mg, 1.87 mmol) in EtOH (4 mL) were treated with piperidine (239 mg, 2.8 mmol), acetic acid (511 mg, 9.35 mmol) and ethyl acetoacetate (487 mg, 3.74 mmol) at room temperature. The reaction mixture was stirred at 90° C. for 3 hours. The mixture was concentrated, quenched with a saturated NaHCO3 solution and extracted with dichloromethane three times. The combined organic layers were combined, dried over K2CO3, filtered and concentrated. The residue was purified on silica gel with methanol (0-10%) in dichloromethane to provide tert-butyl 4-(3-acetyl-2-oxo-2H-pyrano[2,3-b]pyridin-7-yl)-1,4-diazepane-1-carboxylate (450 mg, 62%). MS m/z 388 [M+H]+.

Workup

concentrationThe mixture was concentrated
customquenched with a saturated NaHCO3 solution
extractionextracted with dichloromethane three times
dry with materialdried over K2CO3
filtrationfiltered
concentrationconcentrated
customThe residue was purified on silica gel with methanol (0-10%) in dichloromethane

Sources & evidence

ORD record: ord-11585661b2e34f18b0a9e221dc02c5bd
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09371336B2

Reaction notes

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