Tetrahydrofuran → HCID 57932916, 화합물

HRID 1432658노트

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HRID 1432658 반응식
C1COCC1.Br[C:7]1[N:11]([CH3:12])[N:10]=[CH:9][N:8]=1.[CH2:13]([CH:15]([C:18]1[C:19]2[N:20]([C:25]([C:29]3[S:30][C:31](I)=[CH:32][C:33]=3[O:34][CH3:35])=[C:26]([CH3:28])[N:27]=2)[N:21]=[C:22]([CH3:24])[CH:23]=1)[CH2:16][CH3:17])[CH3:14]>CCOC(C)=O.[Zn].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:13]([CH:15]([C:18]1[C:19]2[N:20]([C:25]([C:29]3[S:30][C:31]([C:7]4[N:11]([CH3:12])[N:10]=[CH:9][N:8]=4)=[CH:32][C:33]=3[O:34][CH3:35])=[C:26]([CH3:28])[N:27]=2)[N:21]=[C:22]([CH3:24])[CH:23]=1)[CH2:16][CH3:17])[CH3:14]

참가 물질

7

반응물 3

HCID 8028Tetrahydrofuran2회HCID 1401211H-1,2,4-Triazole, 5-bromo-1-methyl-HCID 68839933HCID 68839933, 화합물

생성물 1

HCID 57932916HCID 57932916, 화합물수율 62%

시약·촉매·용매 3

HCID 23994Zinc촉매2회HCID 178418397HCID 178418397, 화합물촉매HCID 8857Ethyl Acetate용매

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온도
65 °C

실험 절차

To a slurry of 0.05 g/mL of Reike® Zn in THF (2.8 mL, 2.11 mmol) is added 5-bromo-1-methyl-1H-[1,2,4]triazole and THF (2 mL). The solution is heated at 65° C. for 1 hour, cooled to ambient temperature and the excess Zn allowed to settle for 1 hour. The solution is transferred to a flask containing 8-(1-ethyl-propyl)-3-(5-iodo-3-methoxy-thiophen-2-yl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (0.32 g, 0.70 mmol) and Pd(PPh3)4 (0.041 g, 0.035 mmol). The solution is heated at 65° C. overnight, diluted with EtOAc (30 mL) washed with sat. NH4Cl (30 mL). The aqueous phase is extracted with EtOAc (20 mL). The combined organic layers are dried over MgSO4, filtered and concentrated. The reside is purified by ISCO column chromatography (20%-65% EtOAc/hexane gradient) followed by ISCO column chromatography (100% Et2O) furnish the title compound (0.19 g, 0.46 mmol, 62%). 1H NMR (CDCl3) δ 0.86 (t, J=7.5 Hz, 6H), 1.73-1.91 (m, 4H), 2.51 (s, 3H), 2.52 (s, 3H), 3.26-3.37 (m, 1H), 3.92 (s, 3H), 4.15 (s, 3H), 6.67 (s, 1H), 7.48 (s, 1H), 7.89 (s, 1H). LC/MS (m/z): calcd. for C21H26N6OS (M+H)+: 411.5. found: 411.3.

후처리

  1. temperaturecooled to ambient temperature
  2. customThe solution is transferred to a flask
  3. temperatureThe solution is heated at 65° C. overnight
  4. washwashed with sat. NH4Cl (30 mL)
  5. extractionThe aqueous phase is extracted with EtOAc (20 mL)
  6. dry with materialThe combined organic layers are dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe reside is purified by ISCO column chromatography (20%-65% EtOAc/hexane gradient)

출처 및 근거

ORD 기록
ord-804e14497b294914ab7b68e4149dd0d4
출처 데이터셋
uspto-grants-2009_11
특허 번호
US07612067B2

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