Amantadine → Adamantan-1-yl-[3-(3-thieno[2,3-d]isoxazol-3-yl-phenoxy)-propyl]-amine

HRID 8692

Reaction equation

Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]([C:12]2[C:16]3[S:17][CH:18]=[CH:19][C:15]=3[O:14][N:13]=2)[CH:9]=[CH:10][CH:11]=1.C(=O)([O-])[O-].[K+].[K+].[C:26]12([NH2:36])[CH2:35][CH:30]3[CH2:31][CH:32]([CH2:34][CH:28]([CH2:29]3)[CH2:27]1)[CH2:33]2>C(#N)C>[C:26]12([NH:36][CH2:2][CH2:3][CH2:4][O:5][C:6]3[CH:11]=[CH:10][CH:9]=[C:8]([C:12]4[C:16]5[S:17][CH:18]=[CH:19][C:15]=5[O:14][N:13]=4)[CH:7]=3)[CH2:33][CH:32]3[CH2:31][CH:30]([CH2:29][CH:28]([CH2:34]3)[CH2:27]1)[CH2:35]2

Participants

Conditions

Temperature: 75 °C

Procedure

Mix 3-[3-(3-bromo-propoxy)-phenyl]-thieno[2,3-d]isoxazole (0.250 g, 0.739 mmol), potassium carbonate (0.205 g, 1.48 mmol), 1-adamantanamine (0.560 g, 3.70 mmol) and acetonitrile (4.0 mL) and heat at 75° C., overnight. Cool the reaction mixture and filter through a Waters Sep-Pak (1 g) silica gel cartridge (ethyl acetate). Combine the appropriate fractions and concentrate to give a residue. Purify the residue by column (10 g silica) chromatography using a step gradient from 40% ethyl acetate in dichloromethane to 100% ethyl acetate to 20% methanol in ethyl acetate to give the title compound (132 mg, 44% yield). Purity by LC/MS (APCI)=98%, [M+H]+=409.

Workup

temperatureCool the reaction mixture
filtrationfilter through a Waters Sep-Pak (1 g) silica gel cartridge (ethyl acetate)
concentrationCombine the appropriate fractions and concentrate
customto give a residue
customPurify the residue by column (10 g silica) chromatography

Sources & evidence

ORD record: ord-7b4bedc2459741bd84e5d05b7da325ca
Source dataset: uspto-grants-2006_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07091199B1

Linked notes

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