Cesium carbonate → N-(4-(3-cyclopropylpyridin-2-yloxy)phenyl)benzo[d]thiazol-2-amine

HRID 1880036Notes

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.C(=O)([O-])[O-].[Cs+].[Cs+].[CH:24]1([C:27]2[C:28](F)=[N:29][CH:30]=[CH:31][CH:32]=2)[CH2:26][CH2:25]1>CS(C)=O.CCOC(C)=O>[CH:24]1([C:27]2[C:28]([O:17][C:14]3[CH:15]=[CH:16][C:11]([NH:10][C:2]4[S:1][C:5]5[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=5[N:3]=4)=[CH:12][CH:13]=3)=[N:29][CH:30]=[CH:31][CH:32]=2)[CH2:26][CH2:25]1

Participants

Conditions

Temperature: 125 °C

Procedure

To a solution of 4-(benzo[d]thiazol-2-ylamino)phenol (1.17 g, 4.81 mmol) in DMSO (40 mL) was added cesium carbonate (1.88 g, 5.78 mmol) and 3-cyclopropyl-2-fluoropyridine (660 mg, 4.81 mmol). The resulting mixture was heated to 125° C. for 16 h. After cooling to RT, the reaction mixture was diluted with EtOAc and washed with water and brine several times to remove DMSO. The aqueous layer was back extracted with EtOAc (3×) and the combined organic layer was dried (Na2SO4) and concentrated. The crude product was chromatographed through a Redi-Sep® pre-packed silica gel column (120 g), eluting with a gradient of 0% to 30% EtOAc in hexane, to provide N-(4-(3-cyclopropylpyridin-2-yloxy)phenyl)benzo[d]thiazol-2-amine as tan solid. MS (ESI, pos. ion) m/z: 360.0 (M+1). IC50 (uM) +++++.

Workup

temperatureAfter cooling to RT
washwashed with water and brine several times
customto remove DMSO
extractionThe aqueous layer was back extracted with EtOAc (3×)
dry with materialthe combined organic layer was dried (Na2SO4)
concentrationconcentrated
customThe crude product was chromatographed through a Redi-Sep® pre-packed silica gel column (120 g)
washeluting with a gradient of 0% to 30% EtOAc in hexane

Sources & evidence

ORD record: ord-2cf662d3dc9b405bbdd7bd25e44dc77b
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08318718B2

Reaction notes

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