1,10-Phenanthroline → 1-(1-(7-methoxyquinolin-4-yloxy)propan-2-yl)-5-(thiophen-2-yl)pyridin-2(1H)-one

HRID 1878705Notes

Reaction equation

[OH:1][CH2:2][CH:3]([N:5]1[CH:10]=[C:9]([C:11]2[S:12][CH:13]=[CH:14][CH:15]=2)[CH:8]=[CH:7][C:6]1=[O:16])[CH3:4].I[C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:28][CH3:29])=[CH:25][CH:26]=2)[N:21]=[CH:20][CH:19]=1.C(=O)([O-])[O-].[Cs+].[Cs+].N1C2C(=CC=C3C=2N=CC=C3)C=CC=1>CN(C=O)C.O.CCOC(C)=O.[Cu](I)I>[CH3:29][O:28][C:24]1[CH:23]=[C:22]2[C:27]([C:18]([O:1][CH2:2][CH:3]([N:5]3[CH:10]=[C:9]([C:11]4[S:12][CH:13]=[CH:14][CH:15]=4)[CH:8]=[CH:7][C:6]3=[O:16])[CH3:4])=[CH:19][CH:20]=[N:21]2)=[CH:26][CH:25]=1

Participants

Conditions

Temperature: 140 °C

Procedure

To a solution of 1-(1-hydroxypropan-2-yl)-5-(thiophen-2-yl)pyridin-2(1H)-one (0.052 g, 0.22 mmol) and 4-iodo-7-methoxyquinoline (0.063 g, 0.22 mmol) in 3.0 mL of DMF was added cesium carbonate (Cs2CO3, 0.072 g, 0.22 mmol), 1,10-phenanthroline (0.020 g, 0.11 mmol) followed by copper iodide (CuI) (0.021 g, 0.11 mmol) in a microwave vial. The mixture was heated to 140° C. for 45 minutes. The mixture was then diluted with 40 mL of water and 60 mL of EtOAc. The organic phase was separated, washed with 30 mL of brine, dried over Na2SO4 and concentrated in vacuo. The crude product was purified by a MS-triggered Prep-HPLC to give light organic film 1-(1-(7-methoxyquinolin-4-yloxy)propan-2-yl)-5-(thiophen-2-yl)pyridin-2(1H)-one (0.015 g, 17% yield). MS (ESI pos. ion) m/z (MH+): 393.1. Calc'd Exact Mass for C22H20N2O3S: 392.12.

Workup

customThe organic phase was separated
washwashed with 30 mL of brine
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo
customThe crude product was purified by a MS-triggered Prep-HPLC

Sources & evidence

ORD record: ord-28f5ba49e1774553b660945d2e81e9fe
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08314087B2

Reaction notes

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