Cesium carbonate → HCID 42610018, compound

HRID 474155Notes

Reaction equation

HRID 474155 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([NH:11][C@@H:12]([C:14]2[CH:19]=[CH:18][C:17]([NH:20][CH2:21][C:22]([F:25])([F:24])[F:23])=[CH:16][N:15]=2)[CH3:13])=[O:10])=[CH:4][CH:3]=1.Br[C:27]1[S:28][CH:29]=[CH:30][N:31]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.C(Cl)Cl.[Cu]>[S:28]1[CH:29]=[CH:30][N:31]=[C:27]1[O:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]([NH:11][C@@H:12]([C:14]2[CH:19]=[CH:18][C:17]([NH:20][CH2:21][C:22]([F:25])([F:23])[F:24])=[CH:16][N:15]=2)[CH3:13])=[O:10])=[CH:6][CH:7]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 764302-BromothiazoleHCID 68498915HCID 68498915, compound

Product 1

HCID 42610018HCID 42610018, compoundYield 24.3%

Reagents, catalysts & solvents 3

HCID 23978CopperCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of the starting 2-(4-hydroxyphenyl)-N-((1R)-1-{5-[(2,2,2-trifluoroethyl)amino]pyridin-2-yl}ethyl)acetamide (60.0 mg, 0.17 mmol) in 1.0 ml of dry DMF was added the 2-bromo-1,3-thiazole (30.6 mg, 0.186 mmol), Cs2CO3 (166 mg, 0.508 mmol), and copper powder (1.1 mg, 0.017 mmol). The mixture was irradiated with microwave at 100° C. for 1 h. The mixture was cooled, diluted with CH2Cl2, and washed with saturated sodium bicarbonate solution and brine. The combined aqueous washes were extracted with CH2Cl2. The combined organic phase was dried over Na2SO4, filtered and concentrated in vacuo. Purification by reverse phase chromatography gave 2-[4-(1,3-thiazol-2-yloxy)phenyl]-N-((1R)-1-{5-[(2,2,2-trifluoroethyl)amino]pyridin-2-yl}ethyl)acetamide as a white solid (18 mg, 24%). 1H NMR (CDCl3, 400 MHz) δ 8.227 (d, J=2.75 Hz, 1H); 7.329 (m, 2H); 7.242 (m, 5H); 6.825 (d, J=2.85 Hz, 1H); 6.765 (d, J=7.14 Hz, 1H); 5.106 (quintet, J=6.84 Hz, 1H); 4.381 (dd, J=7.87, 15.93 Hz, 2H); 3.592 (s, 2H); 1.411 (d, J=6.78 Hz, 3H); MS (ES): m/z 438.1 (M+H). FLIPR alpha1I IP=46 nM.

Workup

  1. customThe mixture was irradiated with microwave at 100° C. for 1 h
  2. temperatureThe mixture was cooled
  3. washwashed with saturated sodium bicarbonate solution and brine
  4. extractionThe combined aqueous washes were extracted with CH2Cl2
  5. dry with materialThe combined organic phase was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by reverse phase chromatography

Sources & evidence

ORD record
ord-d8cb7fd6431a4e80a74341294c360f03
Source dataset
uspto-grants-2014_01
Patent number
US08637513B2

Reaction notes

Loading…