Piperazine → Quinazoline

HRID 970454노트

반응식

HRID 970454 반응식
[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[N:3][CH:2]=1.N1CCNCC1.C(N)C1C=CC2OCOC=2C=1.[CH:28]1[CH:29]=[N:30][C:31]([NH:34][S:35]([C:38]2[CH:39]=[CH:40][C:41]([NH2:44])=[CH:42][CH:43]=2)(=[O:37])=[O:36])=[N:32][CH:33]=1.[C:45](Cl)([Cl:47])=[S:46]>N1C=CC=CC=1.O1CCOCC1.ClCCl>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[N:3][CH:2]=1.[Cl-:47].[N:30]1[CH:29]=[CH:28][CH:33]=[N:32][C:31]=1[NH:34][S:35]([C:38]1[CH:43]=[CH:42][C:41]([NH:44][CH:45]=[S:46])=[CH:40][CH:39]=1)(=[O:37])=[O:36]

참가 물질

10

반응물 5

HCID 4837PiperazineHCID 5215SulfadiazineHCID 9210QuinazolineHCID 10040ThiophosgeneHCID 75799Benzo-1,3-dioxole-5-methylamine

생성물 2

HCID 9210QuinazolineHCID 86601004N-Pyrimidin-2-yl-4-thioformylamino-benzenesulfonamide chloride

시약·촉매·용매 3

HCID 1049Pyridine용매HCID 6344Dichloromethane용매HCID 312751,4-Dioxane용매

실험 절차

The synthesis of 4-piperazinylpyrimido[4,5-b]indoles (1b), benzofuranopyrimidines (2b), benzothieno[3,2-d]pyrimidines (3b), and quinazoline (4b) derivatives is depicted in FIG. 20. 4-Chloro-tricyclic and quinazoline building blocks (1a-4a) were synthesized using literature methods. (Pandey, A., et al., J. Med. Chem. 2002, 45:3772-93;Matsuno, K., et al., J. Med. Chem. 2002, 45:3057-66;Matsuno, K., et al., J. Med. Chem. 2002, 45:4513-23;and Venugopalan, B., et al., J. Heterocycl. Chem. 1988, 25:1633-39.) These were converted to the corresponding 4-piperazine derivatives by refluxing with piperazine in pyridine or dioxane. Piperonylamine or sulfadiazine were slowly added to a solution of thiophosgene in dichloromethane while cooling with an ice bath. The resulting mixture was stirred for four hours at room temperature, which gave 1c or 1d, as shown in FIG. 21. Compounds 1c or 1d were further reacted with 4-piperazine-substituted tricyclic or quinazoline derivatives in dichloromethane and stirred overnight at room temperature. To quench excess isothiocyanate, methanol was added, and after removal of solvent, the residue was purified by silica gel chromatography to give compounds 1-7 of FIG. 17 in approximately 20-40% yields.

후처리

  1. temperaturewhile cooling with an ice bath

출처 및 근거

ORD 기록
ord-1fb542469a8d4b6bb831422e27415f40
출처 데이터셋
uspto-grants-2007_12
특허 번호
US07312226B2

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