Potassium tert-butoxide → 1-(azetidin-1-yl)-2-[6-(2-{(1S,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethoxy)pyridin-3-yl)ethanone

HRID 1474742Notes

Reaction equation

HRID 1474742 reaction equation
[CH2:1]([C:3]1[CH:4]=[N:5][C:6]([N:9]2[CH2:14][CH2:13][CH:12]([C@H:15]3[CH2:17][C@H:16]3[CH2:18][CH2:19][OH:20])[CH2:11][CH2:10]2)=[N:7][CH:8]=1)[CH3:2].CC(C)([O-])C.[K+].[N:27]1([C:31](=[O:40])[CH2:32][C:33]2[CH:34]=[N:35][C:36](Cl)=[CH:37][CH:38]=2)[CH2:30][CH2:29][CH2:28]1>CN(C=O)C.CC#N>[N:27]1([C:31](=[O:40])[CH2:32][C:33]2[CH:34]=[N:35][C:36]([O:20][CH2:19][CH2:18][C@@H:16]3[CH2:17][C@@H:15]3[CH:12]3[CH2:13][CH2:14][N:9]([C:6]4[N:7]=[CH:8][C:3]([CH2:1][CH3:2])=[CH:4][N:5]=4)[CH2:10][CH2:11]3)=[CH:37][CH:38]=2)[CH2:30][CH2:29][CH2:28]1

Participants

6

Reactant 3

HCID 23665647Potassium tert-butoxideHCID 1010432321-(Azetidin-1-yl)-2-(6-chloropyridin-3-yl)ethanoneHCID 1176784962-((1S,2R)-2-(1-(5-Ethylpyrimidin-2-yl)piperidin-4-yl)cyclopropyl)ethanol

Product 1

HCID 895839401-(azetidin-1-yl)-2-[6-(2-{(1S,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethoxy)pyridin-3-yl)ethanone

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

2-((1S,2R)-2-(1-(5-Ethylpyrimidin-2-yl)piperidin-4-yl)cyclopropyl)ethanol (40 mg, 0.145 mmol) was dissolved in DMF (2 ml) at RT under N2 and potassium tert-butoxide (0.218 ml, 0.218 mmol) was added. The mixture was stirred at RT for 5 min and 1-(azetidin-1-yl)-2-(6-chloropyridin-3-yl)ethanone (36.7 mg, 0.174 mmol) was added. The mixture was microwaved at 100° C. for 30 min. and 150° C. for 30 min. The mixture was diluted with CH3CN, filtered and purified by reverse-phase HPLC (SunFire Prep C18 OBD Sum 19×100 mm column; 25-95% acetonitrile in 0.1% formic acid in water gradient) to afford the title compound. 1H NMR (500 MHz, CDCl3) δ 8.10 (s, 2H), 8.01 (s, 1H), 7.61 (d, 1H), 6.75 (d, 1H), 4.70 (m, 2H), 4.39 (t, 2H), 4.21 (t, 2H), 4.03 (t, 2H), 3.38 (s, 2H), 2.85 (m, 2H), 2.45 (m, 2H), 2.31 (m, 2H), 2.18 (m, 1H), 1.84 (m, 2H), 1.58 (m, 1H), 1.40 (m, 2H), 1.10-1.20 (m, 5H), 0.95 (m, 2H), 0.68 (m, 2H), −0.40 (m, 1H). LC/MS (m/z): 450 (M+H)+, GPR119 Human EC50: 7.4 nM.

Workup

  1. customThe mixture was microwaved at 100° C. for 30 min. and 150° C. for 30 min
  2. filtrationfiltered
  3. custompurified by reverse-phase HPLC (SunFire Prep C18 OBD Sum 19×100 mm column; 25-95% acetonitrile in 0.1% formic acid in water gradient)

Sources & evidence

ORD record
ord-79df4e7cb1194510a8038b71ff9fe5cb
Source dataset
uspto-grants-2015_04
Patent number
US09018224B2

Reaction notes

Loading…