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 2191995

反応式

HRID 2191995 の反応式
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

参加物

6

反応物 2

HCID 59351351N-(4-(3-chloropyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amineHCID 178419654HCID 178419654、化合物

生成物 1

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

試薬・触媒・溶媒 3

HCID 5483663Ferric acetylacetonate触媒HCID 8028Tetrahydrofuran溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

実験手順

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) +++++.

後処理

  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

出典と根拠

ORDレコード
ord-22ef56b7b4d64c03be61857cc3780a96
出典データセット
uspto-grants-2012_12
特許番号
US08329700B2

関連ノート

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