Water → 1-(5-isopropyl-1H-indazol-4-yl)-4-(5-isopropyl-2-methyl-phenoxymethyl)-3-methyl-isoquinoline

HRID 606306

반응식

HRID 606306 반응식
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([CH2:12][O:13][C:14]2[CH:19]=[C:18]([CH:20]([CH3:22])[CH3:21])[CH:17]=[CH:16][C:15]=2[CH3:23])=[C:4]([CH3:24])[N:3]=1.[CH:25]([C:28]1[CH:36]=[CH:35][C:34]2[NH:33][N:32]=[CH:31][C:30]=2[C:29]=1B(O)O)([CH3:27])[CH3:26].C([O-])([O-])=O.[Na+].[Na+].O>O1CCOCC1.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>[CH:25]([C:28]1[C:29]([C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]([CH2:12][O:13][C:14]3[CH:19]=[C:18]([CH:20]([CH3:22])[CH3:21])[CH:17]=[CH:16][C:15]=3[CH3:23])=[C:4]([CH3:24])[N:3]=2)=[C:30]2[C:34](=[CH:35][CH:36]=1)[NH:33][N:32]=[CH:31]2)([CH3:27])[CH3:26]

참가 물질

7

반응물 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 57358541(5-Isopropyl-1H-indazol-4-yl)boronic acidHCID 866159301-Chloro-4-(5-isopropyl-2-methyl-phenoxymethyl)-3-methyl-isoquinoline

생성물 1

HCID 589946801-(5-isopropyl-1H-indazol-4-yl)-4-(5-isopropyl-2-methyl-phenoxymethyl)-3-methyl-isoquinoline수율 44.1%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

A solution of 1-chloro-4-chloromethyl-3-methyl-isoquinoline (150 mg, 0.66 mmol) is added to a mixture of carvacrol (199 mg, 1.33 mmol) and CsCO3 (645 mg, 1.98 mmol) in DMF (8 ml). After stirring overnight at room temperature, water is added and the mixture is extracted with ether. The combined extracts are washed with saturated brine, dried over Na2SO4, and concentrated in vacuo. The residue is chromatographed on silica gel to give 220 mg of 1-chloro-4-(5-isopropyl-2-methyl-phenoxymethyl)-3-methyl-isoquinoline. A mixture of 1-chloro-4-(5-isopropyl-2-methyl-phenoxymethyl)-3-methyl-isoquinoline (220 mg, 0.65 mmol), 5-isopropylindazole-4-boronic acid (173 mg, 0.85 mmol), Pd(PPh3)4 (38 mg, 0.033 mmol), and Na2CO3 (1.3 ml of 2M in H2O) in dioxane (8 ml) The mixture is heated for 18 h at 100° C. After cooling to room temperature, water is added and the resulting mixture is extracted with EtOAc. The combined extracts are dried over Na2SO4 and concentrated in vacuo. The residue is chromatographed on silica gel to give 133 mg of 1-(5-isopropyl-1H-indazol-4-yl)-4-(5-isopropyl-2-methyl-phenoxymethyl)-3-methyl-isoquinoline

후처리

  1. temperatureAfter cooling to room temperature
  2. extractionthe resulting mixture is extracted with EtOAc
  3. dry with materialThe combined extracts are dried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe residue is chromatographed on silica gel

출처 및 근거

ORD 기록
ord-7c071b245da64bd692950dd1f2cc8b75
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07915288B2

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