Water → 1-Chloro-4-(5-isopropyl-2-methyl-phenoxymethyl)-3-methyl-isoquinoline

HRID 606305

반응식

HRID 606305 반응식
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([CH2:12]Cl)=[C:4]([CH3:14])[N:3]=1.[CH:15]1[C:22]([CH:23]([CH3:25])[CH3:24])=[CH:21][CH:20]=[C:18]([CH3:19])[C:16]=1[OH:17].O>CN(C=O)C>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([CH2:12][O:17][C:16]2[CH:15]=[C:22]([CH:23]([CH3:24])[CH3:25])[CH:21]=[CH:20][C:18]=2[CH3:19])=[C:4]([CH3:14])[N:3]=1

참가 물질

5

반응물 3

HCID 962WaterHCID 10364CarvacrolHCID 866159311-Chloro-4-chloromethyl-3-methyl-isoquinoline

생성물 1

HCID 866159301-Chloro-4-(5-isopropyl-2-methyl-phenoxymethyl)-3-methyl-isoquinoline수율 98.1%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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. extractionthe mixture is extracted with ether
  2. washThe combined extracts are washed with saturated brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe residue is chromatographed on silica gel

출처 및 근거

ORD 기록
ord-05b6e46f60a04df0876e5802e5aa9366
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07915288B2

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