Tetrahydrofuran → HCID 57932916、化合物

HRID 1432658ノート

反応式

HRID 1432658 の反応式
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]

参加物

7

反応物 3

HCID 8028Tetrahydrofuran2 回HCID 1401211H-1,2,4-Triazole, 5-bromo-1-methyl-HCID 68839933HCID 68839933、化合物

生成物 1

HCID 57932916HCID 57932916、化合物収率 62%

試薬・触媒・溶媒 3

HCID 23994Zinc触媒2 回HCID 178418397HCID 178418397、化合物触媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
65 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-804e14497b294914ab7b68e4149dd0d4
出典データセット
uspto-grants-2009_11
特許番号
US07612067B2

反応ノート

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