Diethyl Carbonate → Ethyl 2-oxocyclohexanecarboxylate

HRID 512113Notes

Reaction equation

HRID 512113 reaction equation
[C:1]1(=[O:7])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:8](=O)([O:12]CC)[O:9][CH2:10][CH3:11].[H-].[Na+]>C1COCC1>[O:7]=[C:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[C:8]([O:9][CH2:10][CH3:11])=[O:12]

Participants

5

Reactant 3

HCID 7766Diethyl CarbonateHCID 7967CyclohexanoneHCID 24758Sodium hydride

Product 1

HCID 95543Ethyl 2-oxocyclohexanecarboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The compounds of this invention may be prepared using methods known to those skilled in the art, or the novel methods of this invention. Specifically, the compounds of this invention with Formula I, II or III can be prepared as illustrated by the exemplary reaction in Scheme 1. Reaction of cyclohexanone with diethyl carbonate in THF in the presence of NaH produced ethyl 2-oxocyclohexanecarboxy late. Reaction of ethyl 2-oxocyclohexanecarboxylate with urea at 175-185° C. produced 5,6,7,8-tetrahydroquinazoline-2,4(1H, 3H )-dione. Reaction of 5,6,7,8-tetrahydroquinazoline-2,4(1H, 3H )-dione with hexamethyldisilazane (HMDS) in toluene in the presence of concentrated sulfuric acid, produced the intermediate 2,4-di(trimethylsilyloxy)-5,6,7,8-tetrahydroquinazol. Reaction of 2,4-di(trimethylsilyloxy)-5,6,7,8-tetrahydroquinazoline with methyl 3-(bromomethyl)benzoate in DMF , followed by treatment with 1,4-dioxane and methanol, produced 1-(3-methoxycarbonylbenzyl)-5,6,7,8-tetrahydroquinazoline-2,4(1H,3H )-dione. Treatment of the ester with NaOH in water-methanol produced 1-(3-carboxybenzyl)-5,6,7,8-tetrahydroquinazoline-2,4(1H,3H)-dione. Coupling of the acid with a substituted amine, such as 1-(pyrimidin-2-yl)piperazine, in the presence of coupling agents, such as 2-(7-aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) and N,N-diisopropylethylamine (DIPEA) in DMF, produced the targeted compound 1-(3-(4-(pyrimidin-2-yl)piperazine-1-carbonyl)benzyl)-5,6,7,8-tetrahydroquinazoline-2,4(1H, 3H)-dione.

Workup

  1. customThe compounds of this invention may be prepared
  2. customas illustrated by the exemplary reaction in Scheme 1

Sources & evidence

ORD record
ord-f059d138346640328651117f829f2bc9
Source dataset
uspto-grants-2015_08
Patent number
US09102631B2

Reaction notes

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