Diethyl Malonate → HCID 178440906, compound

HRID 2410033Notes

Reaction equation

HRID 2410033 reaction equation
[CH3:1][C:2]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][N:12]2[C:17](=[O:18])[CH2:16][C:15](=[O:19])[N:14]([C:20]3[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=3)[C:13]2=[O:26])=[CH:7][CH:6]=1)([CH3:4])[CH3:3].C1C=NC=C([N:33]=[C:34]=[O:35])C=1.C(C1C=CC(CN)=CC=1)(C)(C)C.C(OCC)(=O)[CH2:49][C:50]([O:52]CC)=[O:51].[O-]CC.[Na+]>ClCCl.C(O)C.C(OCC)(=O)C>[CH3:4][C:2]([C:5]1[CH:6]=[CH:7][C:8]([CH2:11][N:12]2[C:17](=[O:18])[C:16]([C:34]([NH:33][CH2:49][C:50]([OH:52])=[O:51])=[O:35])=[C:15]([OH:19])[N:14]([C:20]3[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=3)[C:13]2=[O:26])=[CH:9][CH:10]=1)([CH3:1])[CH3:3]

Participants

9

Reactant 5

HCID 7761Diethyl MalonateHCID 2723922Sodium ethoxideHCID 27356554-tert-ButylbenzylamineHCID 27604933-IsocyanatopyridineHCID 68635082HCID 68635082, compound

Product 1

HCID 178440906HCID 178440906, compoundYield 19%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

1-{[4-(1,1-Dimethylethyl)phenyl]methyl}-3-(3-pyridinyl)-2,4,6(1H,3H,5H)-pyrimidinetrione. A mixture of pyridine 3-isocyanate (622 mg, 5.18 mmoles) and 4-t-butylbenzylamine (912 uL, 5.18 mmoles) in dichloromethane (50 mL) was stirred overnight. The urea was purified by flash chromatography (ethyl acetate), taken up in methoxyethanol (10 mL), treated with diethyl malonate (1.0 mL, 6.58 mmoles) and sodium ethoxide (1.0 mL of a 21 molar solution in ethanol) and heated under reflux for 24 hours in an inert atmosphere. The mixture was cooled, diluted with ethyl acetate and washed with brine. The organic solution was evaporated and purified by flash chromatography (10-100% ethyl acetate in hexane) to give the title compound (340 mg, 19%). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.62 (dd, J=4.80, 1.52 Hz, 1 H), 8.48 (d, J=2.02 Hz, 1 H), 7.75 (d, J=8.08 Hz, 1 H), 7.57 (dd, J=8.21, 4.93 Hz, 1 H), 7.29-7.36 (m, 4 H), 3.55 (s, 2 H), 1.26 (s, 9 H).

Workup

  1. customThe urea was purified by flash chromatography (ethyl acetate)
  2. temperatureheated
  3. temperatureunder reflux for 24 hours in an inert atmosphere
  4. temperatureThe mixture was cooled
  5. washwashed with brine
  6. customThe organic solution was evaporated
  7. custompurified by flash chromatography (10-100% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-4ec40927285940f0b153c1309949cc03
Source dataset
uspto-grants-2014_08
Patent number
US08815884B2

Reaction notes

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