Cesium carbonate → 1-Methyl-4-(2-(4-(pyridin-2-ylamino)phenoxy)pyridin-3-yl)piperidin-2-one

HRID 473724Notes

Reaction equation

F[C:2]1[C:7]([CH:8]2[CH2:13][CH2:12][N:11]([CH3:14])[C:10](=[O:15])[CH2:9]2)=[CH:6][CH:5]=[CH:4][N:3]=1.[N:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[NH:22][C:23]1[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CN1CCCC1=O>CCOC(C)=O>[CH3:14][N:11]1[CH2:12][CH2:13][CH:8]([C:7]2[C:2]([O:29][C:26]3[CH:25]=[CH:24][C:23]([NH:22][C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][N:16]=4)=[CH:28][CH:27]=3)=[N:3][CH:4]=[CH:5][CH:6]=2)[CH2:9][C:10]1=[O:15]

Participants

Conditions

Temperature: 100 °C

Procedure

4-(2-Fluoropyridin-3-yl)-1-methylpiperidin-2-one (0.07 g, 0.33 mmol), 4-(pyridin-2-ylamino)phenol (0.144 g, 0.77 mmol), cesium carbonate (0.274 g, 0.84 mmol), and 1-methyl-2-pyrrolidinone (1 mL) were combined in a sealed tube and heated at 100° C. for 18 h. The cooled mixture was diluted with EtOAc and washed with water; the aqueous layer was back-washed with EtOAc (1×). The combined organic extracts were dried (MgSO4), filtered, and concentrated in vacuo. ISCO purification with 20% to 80% EtOAc (10% MeOH)/Hexanes afforded 1-methyl-4-(2-(4-(pyridin-2-ylamino)phenoxy)pyridin-3-yl)piperidin-2-one (0.053 g, 42.1% yield) as a tan amorphous solid. MS (ESI, pos. ion) m/z: 375.0 (M+1). IC50 (uM) 0.005.

Workup

washwashed with water
washthe aqueous layer was back-washed with EtOAc (1×)
dry with materialThe combined organic extracts were dried (MgSO4)
filtrationfiltered
concentrationconcentrated in vacuo
customISCO purification with 20% to 80% EtOAc (10% MeOH)/Hexanes

Sources & evidence

ORD record: ord-2a31b21141304e1e8a2c02c60f2c6fad
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08637500B2

Reaction notes

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