Water → 2-[2-(4-Cyclobutylpiperazin-1-yl)-2-oxoethyl]-6-(cyclopentyloxy)-1,2,3,4-tetrahydroisoquinoline

HRID 1713081Notes

Reaction equation

[CH:1]1([N:5]2[CH2:10][CH2:9][N:8]([C:11](=[O:24])[CH2:12][N:13]3[CH2:22][CH2:21][C:20]4[C:15](=[CH:16][CH:17]=[C:18]([OH:23])[CH:19]=4)[CH2:14]3)[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.Br[CH:26]1[CH2:30][CH2:29][CH2:28][CH2:27]1.C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[CH:1]1([N:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:24])[CH2:12][N:13]3[CH2:22][CH2:21][C:20]4[C:15](=[CH:16][CH:17]=[C:18]([O:23][CH:26]5[CH2:30][CH2:29][CH2:28][CH2:27]5)[CH:19]=4)[CH2:14]3)[CH2:9][CH2:10]2)[CH2:4][CH2:3][CH2:2]1

Participants

Conditions

Temperature: 50 °C

Procedure

To a stirred solution of 2-[2-(4-cyclobutylpiperazin-1-yl)-2-oxoethyl]-1,2,3,4-tetrahydroisoquinolin-6-ol (145 mg, 0.44 mmol) in DMF (10.0 ml) is added 1-bromo-cyclopentane (72 mg, 0.48 mmol), and K2CO3 (60 mg, 0.44 mmol). The resulting mixture is stirred at 50° C. overnight. Water (10.0 ml) is added to quench the reaction, and the mixture is extracted with DCM (10 ml×3). The combined organic phase is dried over sodium sulfate, and the solvent is removed under reduced pressure to give a residue that is purified by PTLC (EtOAc/4% TEA) to give the title compound. 1H NMR (300 MHz, CDCl3) δ 6.84-6.94 (1H, m), 6.60-6.70 (2H, m), 4.68-4.74 (1H, m), 3.60-3.74 (6H, m), 3.36 (2H, s), 2.62-2.86 (5H, m), 2.22-2.34 (4H, m), 1.56˜2.10 (14H, m); MS (+VE) m/z 398.3 (M++1).

Workup

customto quench
customthe reaction
extractionthe mixture is extracted with DCM (10 ml×3)
dry with materialThe combined organic phase is dried over sodium sulfate
customthe solvent is removed under reduced pressure
customto give a residue that
customis purified by PTLC (EtOAc/4% TEA)

Sources & evidence

ORD record: ord-fbfc9d28c4f04593988957b683b4b3a8
Source dataset: uspto-grants-2010_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07795262B2

Reaction notes

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