Triethylamine → 2-(Naphthalen-1-ylmethyl)-9-(quinoxalin-2-yl)-2,9-diazaspiro[5.5]undecan-1-one

HRID 41542

Reaction equation

Cl.[C:2]1([N:12]2[CH:17](C)[CH2:16][CH2:15][C:14]3([CH2:23][CH2:22][NH:21][CH2:20][CH2:19]3)[C:13]2=[O:24])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][CH:3]=1.Cl[C:26]1[CH:35]=[N:34][C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[N:27]=1.[CH2:36](N(CC)CC)C>CCO>[C:11]1([CH2:2][N:12]2[CH2:17][CH2:16][CH2:15][C:14]3([CH2:19][CH2:20][N:21]([C:26]4[CH:35]=[N:34][C:33]5[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=5)[N:27]=4)[CH2:22][CH2:23]3)[C:13]2=[O:24])[C:6]2[C:7](=[CH:8][CH:3]=[CH:4][CH:5]=2)[CH:36]=[CH:9][CH:10]=1

Participants

Conditions

Temperature: 160 °C

Procedure

Crude 2-naphthalen-1-yl-methyl-2,9-diaza-spiro[5.5]undecan-1-one hydrochloride (100 mg, 0.29 mmol), 2-chloro-quinoxaline (81 mg, 0.49 mmol) and triethylamine (0.12 ml, 0.87 mmol) were dissolved in EtOH (1 ml) in a microwave tube. The tube was sealed and the suspension was heated at 160° C. over 20 min under microwave conditions. The solvent was removed under reduced pressure and the resulting crude product was purified by preparative reverse phase chromatography (Sun Fire C18 column, 16 min linear gradient: elution 20-60% (CH3CN in H2O (0.1% TFA)); flow rate 50 ml/min) to yield 87 mg (53%) of the title compound. [1H NMR (DMSO, 600 MHz) δ 8.86 (s, 1H), 8.07-8.00 (m, 1H), 7.98-7.91 (m, 1H), 7.86 (d, 1H, J=8.28 Hz), 7.82 (d, 1H, J=8.02 Hz), 7.64-7.56 (m, 2H), 7.56-7.50 (m, 2H), 7.48 (t, 1H), 7.38 (t, 1H), 7.34 (d, 1H, J=7.06 Hz), 4.98 (s, 2H), 4.37-4.26 (m, 2H), 3.46 (t, 2H), 3.23-3.10 (m, 2H), 2.20-2.08 (m, 2H), 1.93-1.82 (m, 2H), 1.80-1.70 (m, 2H), 1.67-1.53 (m, 2H), LCMS RtD=3.10 min, [M+H]+=437.2].

Workup

customThe tube was sealed
customThe solvent was removed under reduced pressure
customthe resulting crude product was purified by preparative reverse phase chromatography (Sun Fire C18 column, 16 min linear gradient: elution 20-60% (CH3CN in H2O (0.1% TFA)); flow rate 50 ml/min)

Sources & evidence

ORD record: ord-4ae20f03f4a34420a6c9c32528453826
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08530648B2

Linked notes

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