Cesium carbonate → 4-(2-(4-(Benzo[d]thiazol-2-ylamino)phenoxy)pyridin-3-yl)-1-methylpyrrolidin-2-one

HRID 410268Notes

Reaction equation

HRID 410268 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[S:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[N:9]=[C:8]1[NH:16][C:17]1[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=1.F[C:25]1[C:30]([CH:31]2[CH2:35][N:34]([CH3:36])[C:33](=[O:37])[CH2:32]2)=[CH:29][CH:28]=[CH:27][N:26]=1>CN1C(=O)CCC1>[S:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[N:9]=[C:8]1[NH:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][C:25]2[C:30]([CH:31]3[CH2:35][N:34]([CH3:36])[C:33](=[O:37])[CH2:32]3)=[CH:29][CH:28]=[CH:27][N:26]=2)=[CH:19][CH:18]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 593268134-(Benzo[d]thiazol-2-ylamino)phenolHCID 593270184-(2-Fluoropyridin-3-yl)-1-methylpyrrolidin-2-one

Product 1

HCID 593270454-(2-(4-(Benzo[d]thiazol-2-ylamino)phenoxy)pyridin-3-yl)-1-methylpyrrolidin-2-oneYield 73.1%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of cesium carbonate (0.625 g, 1.92 mmol), 4-(benzo[d]thiazol-2-ylamino)phenol (0.445 g, 1.84 mmol), and 4-(2-fluoropyridin-3-yl)-1-methylpyrrolidin-2-one (0.111 g, 0.572 mmol) was added NMP (2 mL). The reaction mixture was degassed and heated to 100° C. for 30 min, heated to 120° C. for 3.5 h, and diluted with EtOAc and water. The aqueous phase was extracted with EtOAc (3×), and the combined organic extracts were washed with 1 M NaOH (1×), brine (1×), dried over MgSO4, filtered, and concentrated. Purification by flash column chromatography on silica gel (20% to 80% EtOAc (10% MeOH) in hexanes) gave 4-(2-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyridin-3-yl)-1-methylpyrrolidin-2-one (0.174 g, 0.418 mmol, 73% yield) as a white solid and a 1:1 mixture of enantiomers. MS (ESI, pos. ion) m/z: 417.1 (M+1). IC50 (uM) +++++.

Workup

  1. customThe reaction mixture was degassed
  2. temperatureheated to 120° C. for 3.5 h
  3. additiondiluted with EtOAc and water
  4. extractionThe aqueous phase was extracted with EtOAc (3×)
  5. washthe combined organic extracts were washed with 1 M NaOH (1×), brine (1×)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by flash column chromatography on silica gel (20% to 80% EtOAc (10% MeOH) in hexanes)

Sources & evidence

ORD record
ord-124064e30cad434eb3edb107f75c5679
Source dataset
uspto-grants-2014_06
Patent number
US08759532B2

Reaction notes

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