Sodium ethoxide → tert-butyl 2-(diethylamino)-4-oxo-5,6,7,9-tetrahydro-1H-pyrimido[4,5-c]azepine-8-carboxylate

HRID 72795Notes

Reaction equation

HRID 72795 reaction equation
C(O[C:4]([CH:6]1[CH2:12][CH2:11][CH2:10][N:9]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:8][C:7]1=O)=[O:5])C.FC(F)(F)C([O-])=O.[CH2:28]([N+:30]([CH2:34][CH3:35])=[C:31]([NH2:33])[NH2:32])[CH3:29].[O-]CC.[Na+]>CCO.O>[C:16]([O:15][C:13]([N:9]1[CH2:10][CH2:11][CH2:12][C:6]2[C:4]([OH:5])=[N:32][C:31]([N:30]([CH2:34][CH3:35])[CH2:28][CH3:29])=[N:33][C:7]=2[CH2:8]1)=[O:14])([CH3:17])([CH3:18])[CH3:19]

Participants

6

Reactant 3

HCID 2723922Sodium ethoxideHCID 574799101-Tert-butyl 4-ethyl 3-oxoazepane-1,4-dicarboxylateHCID 131731834Diethyl guanidinium trifluoroacetate

Product 1

HCID 178463889tert-butyl 2-(diethylamino)-4-oxo-5,6,7,9-tetrahydro-1H-pyrimido[4,5-c]azepine-8-carboxylateYield 43%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

To a solution of 3-oxo-azepane-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester (0.67 g, 2.3 mmol) in EtOH (10 mL) was added diethyl guanidinium trifluoroacetate (0.54 g, 2.3 mmol) and sodium ethoxide (21 wt % in EtOH, 2.3 mL). The reaction was heated at reflux for 16 h then cooled to room temperature (rt). The reaction mixture was diluted with H2O and extracted with CH2Cl2 (2×). The combined organic extracts were dried and concentrated. The resulting material was triturated with hexanes/Et2O (9:1) to give the title compound (0.334 mg, 43%) as a light brown solid. MS (ESI): mass calcd. for C17H28N4O3, 336.4; m/z found, 337.4 [M+H]+. 1H NMR (CDCl3): 4.34-4.25 (m, 2H), 3.62-3.46 (m, 6H), 2.66-2.58 (m, 2H), 1.88-1.77 (m, 2H), 1.50-1.36 (m, 9H), 1.21-1.14 (m, 6H).

Workup

  1. temperatureThe reaction was heated
  2. temperatureat reflux for 16 h
  3. extractionextracted with CH2Cl2 (2×)
  4. customThe combined organic extracts were dried
  5. concentrationconcentrated
  6. customThe resulting material was triturated with hexanes/Et2O (9:1)

Sources & evidence

ORD record
ord-ac4394c2415f4bf999182c14930e4a04
Source dataset
uspto-grants-2014_09
Patent number
US08829011B2

Reaction notes

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