Sulfuric Acid → 1-(3-methoxycarbonylbenzyl)-5,6,7,8-tetrahydroquinazoline-2,4(1H,3H)-dione

HRID 512115Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 512115
[NH:1]1[C:10]2[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=2[C:4](=[O:11])[NH:3][C:2]1=[O:12].C[Si](C)(C)N[Si](C)(C)C.S(=O)(=O)(O)O.C[Si](C)(C)OC1N=C(O[Si](C)(C)C)C2CCCCC=2N=1.Br[CH2:48][C:49]1[CH:50]=[C:51]([CH:56]=[CH:57][CH:58]=1)[C:52]([O:54][CH3:55])=[O:53]>C1(C)C=CC=CC=1.CN(C=O)C.CO.O1CCOCC1>[CH3:55][O:54][C:52]([C:51]1[CH:50]=[C:49]([CH:58]=[CH:57][CH:56]=1)[CH2:48][N:1]1[C:10]2[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=2[C:4](=[O:11])[NH:3][C:2]1=[O:12])=[O:53]

Komponenten

10

Edukt 5

HCID 1118Sulfuric AcidHCID 13838HexamethyldisilazaneHCID 4718725,6,7,8-Tetrahydroquinazoline-2,4(1H,3H)-dioneHCID 517981Methyl 3-(bromomethyl)benzoateHCID 12514465HCID 12514465, Verbindung

Produkt 1

HCID 895453961-(3-methoxycarbonylbenzyl)-5,6,7,8-tetrahydroquinazoline-2,4(1H,3H)-dione

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 887MethanolLösungsmittelHCID 1140TolueneLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

  1. customproduced the intermediate 2,4-di(trimethylsilyloxy)-5,6,7,8-tetrahydroquinazol

Quellen und Nachweise

ORD-Eintrag
ord-7aeee6a0c4ba4c34add08535d63e23e9
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09102631B2

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