N-(4-(3-chloropyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine → N-(4-(3-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine

HRID 555867

Reaction equation

HRID 555867 reaction equation
Cl[C:2]1[C:3]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]3[S:17][C:18]4[CH:24]=[CH:23][CH:22]=[CH:21][C:19]=4[N:20]=3)=[CH:11][CH:10]=2)=[N:4][CH:5]=[CH:6][N:7]=1.[O:25]1[CH2:30][CH2:29][CH:28]([Mg]Br)[CH2:27][CH2:26]1>C1COCC1.CN1C(=O)CCC1.C/C(/[O-])=C/C(C)=O.C/C(/[O-])=C/C(C)=O.C/C(/[O-])=C/C(C)=O.[Fe+3]>[O:25]1[CH2:30][CH2:29][CH:28]([C:2]2[C:3]([O:8][C:9]3[CH:14]=[CH:13][C:12]([NH:15][C:16]4[S:17][C:18]5[CH:24]=[CH:23][CH:22]=[CH:21][C:19]=5[N:20]=4)=[CH:11][CH:10]=3)=[N:4][CH:5]=[CH:6][N:7]=2)[CH2:27][CH2:26]1

Participants

6

Reactant 2

HCID 59351351N-(4-(3-chloropyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amineHCID 178419654HCID 178419654, compound

Product 1

HCID 59351180N-(4-(3-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine

Reagents, catalysts & solvents 3

HCID 5483663Ferric acetylacetonateCatalystHCID 8028TetrahydrofuranSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a round bottomed flask was added N-(4-(3-chloropyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine (0.3000 g, 0.846 mmol) dissolved in a mixture of THF (1.353 mL) and NMP (0.338 mL). Iron(III)acetylacetonate (0.015 g, 0.042 mmol) was added and the temperature was brought to 0° C. (Tetrahydro-2H-pyran-4-yl)magnesium bromide (3.70 mL, 2.96 mmol) was added dropwise to the reaction. The reaction was quenched with sat. ammonium chloride. The reaction mixture was diluted with water and extracted with EtOAc. The organic extract was washed with water, brine, dried with magnesium sulfate, filtered, and concentrated. LC showed formation of N-(4-(3-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine and N-(4-(pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage pre-packed silica gel column (40S), eluting with a gradient of 1% to 5% MeOH in DCM, to provide N-(4-(3-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine. MS (ESI, pos. ion) m/z: 405.0 (M+1). IC50 (uM) +++++.

Workup

  1. customwas brought to 0° C.
  2. additionwas added dropwise to the reaction
  3. customThe reaction was quenched with sat. ammonium chloride
  4. additionThe reaction mixture was diluted with water
  5. extractionextracted with EtOAc
  6. extractionThe organic extract
  7. washwas washed with water, brine
  8. dry with materialdried with magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customchromatographed through a Biotage pre-packed silica gel column (40S)
  12. washeluting with a gradient of 1% to 5% MeOH in DCM

Sources & evidence

ORD record
ord-86beb4d0ad9b404dbf337a08496b1a48
Source dataset
uspto-grants-2011_11
Patent number
US08053438B2

Linked notes

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