Cesium carbonate → HCID 67417834, compound

HRID 2373926Notes

Reaction equation

HRID 2373926 reaction equation
[NH2:1][C:2]1[C:3]2[N:4]([C:8]([CH:18]3[CH2:21][CH2:20][CH2:19]3)=[N:9][C:10]=2[C:11]2[CH:12]=[C:13]([OH:17])[CH:14]=[CH:15][CH:16]=2)[CH:5]=[CH:6][N:7]=1.[C:22](=O)([O-:24])[O-:23].[Cs+].[Cs+].Br[CH2:29][CH2:30][OH:31].C([O-])(O)=O.[Na+]>CN(C=O)C>[CH:22]([OH:24])=[O:23].[NH2:1][C:2]1[C:3]2[N:4]([C:8]([CH:18]3[CH2:21][CH2:20][CH2:19]3)=[N:9][C:10]=2[C:11]2[CH:12]=[C:13]([CH:14]=[CH:15][CH:16]=2)[O:17][CH2:29][CH2:30][OH:31])[CH:5]=[CH:6][N:7]=1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 108982-BromoethanolHCID 516892Sodium BicarbonateHCID 11716093HCID 11716093, compound

Product 1

HCID 67417834HCID 67417834, compoundYield 12%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

To a solution of 3-(8-amino-3-cyclobutyl-imidazo[1,5-a]pyrazin-1-yl)-phenol (28 mg, 0.1 mmol) in anhydrous DMF (1 ml) was added cesium carbonate (49 mg, 0.15 mmol) followed by a solution of 2-bromoethanol (12.5 mg, 0.1 mmol) in DMF (0.5 ml). The reaction was stirred at 60° C. overnight. The reaction was poured onto saturated NaHCO3 (10 ml) and extracted with EtOAc (2×10 ml). The combined organics were washed with water (10 ml) and aqueous brine solution (3×10 ml), dried (MgSO4), filtered and concentrated in vacuo. Purification by mass-directed HPLC gave 2-[3-(8-Amino-3-cyclobutyl-imidazo[1,5-a]pyrazin-1-yl)-phenoxy]-ethanol formic acid salt (4.0 mg, 12%) as an off-white solid: 1H NMR (400 MHz, CD3OD) δ 8.54 (s, 1H), 7.48-7.41 (m, 2H), 7.13-7.09 (m, 2H), 7.01 (d, 1H, J=10.3 Hz), 6.93 (d, 1H, J=5.8 Hz), 4.14 (t, 2H, J=4.9 Hz), 4.03-3.97 (m, 1H), 3.92 (t, 2H, J=4.9 Hz), 2.61-2.51 (m, 4H), 2.15-2.10 (m, 1H), 2.06-2.01 (m, 1H), 3H not observed (NH2 & OH); LCMS (ES+) m/z 325.08 [MH+] at Rt 2.39 min.

Workup

  1. extractionextracted with EtOAc (2×10 ml)
  2. washThe combined organics were washed with water (10 ml) and aqueous brine solution (3×10 ml)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by mass-directed HPLC

Sources & evidence

ORD record
ord-c2de45aaa0e24a709aaf02f9289404c9
Source dataset
uspto-grants-2008_12
Patent number
US07459554B2

Reaction notes

Loading…