4-Iodo-1-tritylimidazole → 2-phenyl-5-(1-trityl-1H-imidazol-4-yl)pyrimidine

HRID 42298

반응식

HRID 42298 반응식
I[C:2]1[N:3]=[CH:4][N:5]([C:7]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=1.C([Mg]Br)C.Br[C:31]1[CH:32]=[N:33][C:34]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[N:35][CH:36]=1>C1COCC1.ClCCl.[Cl-].[Zn+2].[Cl-].[Pd]>[C:37]1([C:34]2[N:33]=[CH:32][C:31]([C:2]3[N:3]=[CH:4][N:5]([C:7]([C:8]4[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=4)([C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=4)[C:14]4[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=4)[CH:6]=3)=[CH:36][N:35]=2)[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1

참가 물질

8

반응물 3

HCID 6182524-Iodo-1-tritylimidazoleHCID 143877455-Bromo-2-phenylpyrimidineHCID 178418443HCID 178418443, 화합물

생성물 1

HCID 592524592-phenyl-5-(1-trityl-1H-imidazol-4-yl)pyrimidine

시약·촉매·용매 4

HCID 23938Palladium촉매HCID 3007855Zincchloride촉매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

반응 조건

온도
70 °C

실험 절차

To a solution of 4-Iodo-1-trityl-1H-imidazole (Synthonix, 2.0 g, 4.58 mmol) in THF (50 mL) at room temperature was added ethylmagnesium bromide (Aldrich, 1.0 M solution in THF, 5.5 mL, 5.50 mmol) under dry conditions. After stirring for 90 minutes, zinc chloride (Aldrich, 0.749. g, 5.50 mmol) was added to the reaction mixture. After stirring for an additional 90 minutes, tetrakis(triphenyl)phosphine)palladium (Strem, 0.529 g, 0.46 mmol) and 5-bromo-2-phenylpyrimidine (as prepared in Example 1, step A, 1.29 g, 5.50 mmol) were added to the reaction mixture. The reaction mixture was heated in a 70° C. oil bath overnight. Upon cooling, the reaction was diluted with dichloromethane and washed with 0.5 M EDTA buffer (at pH ˜9) (2×250 mL) followed by brine (150 mL). The organics were dried over sodium sulfate, filtered, and concentrated. The crude product was purified by flash silica column chromatography using an 80 g Silicycle® column (elution with 10-30% ethyl acetate in hexane) which afforded the desired intermediate, 2-phenyl-5-(1-trityl-1H-imidazol-4-yl)pyrimidine, as a white solid (1.38 g, 65%). Rf 0.87 with 95:5 v/v dichloromethane-methanol; 1H-NMR (400 MHz; DMSO-d6) δ 9.29 (s, 2H), 8.42 (m, 2H), 7.92 (d, 1H), 7.62 (d, 1H), 7.56-7.43 (m, 13H), 7.24-7.22 (m, 6H); MS (ESI−) m/z 463.0 (M−1); H-PGDS FPBA IC50: >20 μM.

후처리

  1. stirringAfter stirring for an additional 90 minutes
  2. temperatureUpon cooling
  3. washwashed with 0.5 M EDTA buffer (at pH ˜9) (2×250 mL)
  4. dry with materialThe organics were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by flash silica column chromatography
  8. washan 80 g Silicycle® column (elution with 10-30% ethyl acetate in hexane) which

출처 및 근거

ORD 기록
ord-4efe0042766d459ab4f9c536c728c18f
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08536185B2

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