N-Methyl-o-phenylenediamine → trans-2-(2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-(methylthio)pyrimidin-4-yl)cyclopropyl)-1-methyl-1H-benzo[d]imidazole

HRID 1498779노트

반응식

HRID 1498779 반응식
[CH3:1][NH:2][C:3]1[C:4]([NH2:9])=[CH:5][CH:6]=[CH:7][CH:8]=1.C[Al](C)C.C(O[C:17]([C@@H:19]1[CH2:21][C@H:20]1[C:22]1[CH:27]=[C:26]([N:28]2[C:32]([CH3:33])=[N:31][C:30]([CH3:34])=[N:29]2)[N:25]=[C:24]([S:35][CH3:36])[N:23]=1)=O)C>C1(C)C=CC=CC=1>[CH3:34][C:30]1[N:31]=[C:32]([CH3:33])[N:28]([C:26]2[N:25]=[C:24]([S:35][CH3:36])[N:23]=[C:22]([C@@H:20]3[CH2:21][C@H:19]3[C:17]3[N:2]([CH3:1])[C:3]4[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=4[N:9]=3)[CH:27]=2)[N:29]=1

참가 물질

5

반응물 3

HCID 78498N-Methyl-o-phenylenediamineHCID 16682925TrimethylaluminumHCID 86732038ethyl-trans-2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-(methylthio)pyrimidin-4-yl)cyclopropanecarboxylate

생성물 1

HCID 71547705trans-2-(2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-(methylthio)pyrimidin-4-yl)cyclopropyl)-1-methyl-1H-benzo[d]imidazole

시약·촉매·용매 1

HCID 1140Toluene용매2회

반응 조건

온도
130 °C

실험 절차

To N1-methylbenzene-1,2-diamine (2.01 g, 16.5 mmol, 1.1 eq.) dissolved in toluene (20 mL) was added trimethylaluminium solution (2.0 M in toluene, 22.5 mL, 44.98 mmol, 3.0 eq.) under nitrogen at 0° C. dropwise. The reaction was stirred at a temperature between 10° C. to 20° C. for 30 minutes followed by the addition of ethyl-trans-2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-(methylthio)pyrimidin-4-yl)cyclopropanecarboxylate (1-4) (5.00 g, 14.99 mmol, 1.0 eq.) in toluene (80 mL) and the reaction was heated to 130° C. for 12 hours. The reaction was cooled to room temperature and quenched with saturated sodium bicarbonate (100 mL) then extracted with ethyl acetate (3×200 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrate to dryness. The crude product was purified by silica gel column chromatography (0-30% acetone in dichloromethane) to afford trans-2-(2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-(methylthio)pyrimidin-4-yl)cyclopropyl)-1-methyl-1H-benzo[d]imidazole (1-5) as a pale pink solid. 1H NMR (400 MHz, CDCl3) δ 7.72-7.67 (m, 1H), 7.56 (s, 1H), 7.31-7.22 (m, 3H), 3.81 (s, 3H), 2.90 (s, 3H), 2.86-2.76 (m, 2H), 2.59 (s, 3H), 2.40 (s, 3H), 2.06-1.97 (m, 2H). LRMS m/z (M+H) 392 found, 392 required. m.p. 157-159° C.

후처리

  1. temperatureThe reaction was cooled to room temperature
  2. customquenched with saturated sodium bicarbonate (100 mL)
  3. extractionthen extracted with ethyl acetate (3×200 mL)
  4. dry with materialThe combined organic layers were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrate to dryness
  7. customThe crude product was purified by silica gel column chromatography (0-30% acetone in dichloromethane)

출처 및 근거

ORD 기록
ord-adb604f325884fa0a8f9287fe26d1732
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09200001B2

반응 노트

불러오는 중…