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

HRID 512115노트

반응식

HRID 512115 반응식
[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]

참가 물질

10

반응물 5

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

생성물 1

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

시약·촉매·용매 4

HCID 887Methanol용매HCID 1140Toluene용매HCID 6228Dimethylformamide용매HCID 312751,4-Dioxane용매

실험 절차

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.

후처리

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

출처 및 근거

ORD 기록
ord-7aeee6a0c4ba4c34add08535d63e23e9
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09102631B2

반응 노트

불러오는 중…