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

HRID 606306

Reaction equation

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]

Participants

Conditions

Temperature: 100 °C

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

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

Sources & evidence

ORD record: ord-7c071b245da64bd692950dd1f2cc8b75
Source dataset: uspto-grants-2011_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07915288B2

Linked notes

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