Cesium carbonate → HCID 59351199, compound

HRID 555884Notes

Reaction equation

HRID 555884 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1.F[C:19]1[C:20]([CH:25]2[CH2:30][CH2:29][N:28]([C:31](=[O:33])[CH3:32])[CH2:27][CH2:26]2)=[N:21][CH:22]=[CH:23][N:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][C:19]2[C:20]([CH:25]3[CH2:26][CH2:27][N:28]([C:31](=[O:33])[CH3:32])[CH2:29][CH2:30]3)=[N:21][CH:22]=[CH:23][N:24]=2)=[CH:13][CH:12]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 593268134-(Benzo[d]thiazol-2-ylamino)phenolHCID 593512871-(4-(3-Fluoropyrazin-2-yl)piperidin-1-yl)ethanone

Product 1

HCID 59351199HCID 59351199, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

Procedure

The mixture of 4-(benzo[d]thiazol-2-ylamino)phenol (91 mg, 0.38 mmol), 1-(4-(3-fluoropyrazin-2-yl)piperidin-1-yl)ethanone (56 mg, 0.25 mmol), and cesium carbonate (123 mg, 0.38 mmol) in DMSO (0.85 mL) was heated at 80° C. for 16 h. After cooling to RT, the reaction mixture was partitioned between Teac and brine. The aqueous layer was back extracted with Teac (2×) and the combined organic layer was dried (Na2SO4) and concentrated. The crude material was purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g), eluting with a gradient of 0% to 100% Teac in hexane, then 3% MeOH in Teac, followed by reverse-phase preparative HPLC using a Germini C18 5 uM column, 0.1% TFA in CH3CN/H2O, gradient 10% to 100% over 15 min, then neutralize with Si carbonate resin, to provide 1-(4-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)piperidin-1-yl) as a white solid. MS (ESI, pos. ion) m/z: 445.9 (M+1). IC50 (uM) +++++.

Workup

  1. temperatureAfter cooling to RT
  2. customthe reaction mixture was partitioned between Teac and brine
  3. extractionThe aqueous layer was back extracted with Teac (2×)
  4. dry with materialthe combined organic layer was dried (Na2SO4)
  5. concentrationconcentrated
  6. customThe crude material was purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g)
  7. washeluting with a gradient of 0% to 100% Teac in hexane
  8. customover 15 min
  9. customto provide 1-(4-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)piperidin-1-yl) as a white solid

Sources & evidence

ORD record
ord-87d08f08963248c1b04666ddbb8f3cab
Source dataset
uspto-grants-2011_11
Patent number
US08053438B2

Reaction notes

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