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

HRID 606305

Reaction equation

HRID 606305 reaction equation
[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

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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

Workup

  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

Sources & evidence

ORD record
ord-05b6e46f60a04df0876e5802e5aa9366
Source dataset
uspto-grants-2011_03
Patent number
US07915288B2

Linked notes

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