Tetrahydrofuran → N2-(benzo[d]thiazol-6-yl)-N4-isopropyl-5-(5-((1-(methylsulfonyl)piperidin-4-yl)amino)-1,3,4-oxadiazol-2-yl)pyridine-2,4-diamine

HRID 595502Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 595502
[S:1]1[C:5]2[CH:6]=[C:7]([NH:10][C:11]3[CH:16]=[C:15]([NH:17][CH:18]([CH3:20])[CH3:19])[C:14]([C:21]4[O:22][C:23]([NH:26][CH:27]5[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]5)=[N:24][N:25]=4)=[CH:13][N:12]=3)[CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.C1COCC1.CCN(C(C)C)C(C)C.[S:47](Cl)([CH3:50])(=[O:49])=[O:48]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[S:1]1[C:5]2[CH:6]=[C:7]([NH:10][C:11]3[CH:16]=[C:15]([NH:17][CH:18]([CH3:20])[CH3:19])[C:14]([C:21]4[O:22][C:23]([NH:26][CH:27]5[CH2:32][CH2:31][N:30]([S:47]([CH3:50])(=[O:49])=[O:48])[CH2:29][CH2:28]5)=[N:24][N:25]=4)=[CH:13][N:12]=3)[CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1

Komponenten

7

Edukt 4

HCID 8028TetrahydrofuranHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 89690939N2-(benzo[d]thiazol-6-yl)-N4-isopropyl-5-(5-(piperidin-4-ylamino)-1,3,4-oxadiazol-2-yl)pyridine-2,4-diamine

Produkt 1

HCID 89690810N2-(benzo[d]thiazol-6-yl)-N4-isopropyl-5-(5-((1-(methylsulfonyl)piperidin-4-yl)amino)-1,3,4-oxadiazol-2-yl)pyridine-2,4-diamine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

To a stirred solution of N2-(benzo[d]thiazol-6-yl)-N4-isopropyl-5-(5-(piperidin-4-ylamino)-1,3,4-oxadiazol-2-yl)pyridine-2,4-diamine (Example 131) (30 mg, 0.06 mmol) in DCM (4 mL): THF (4 mL), added DIPEA (0.09 mmol, 1.5 equiv.) and DMAP (0.006 mmol, 0.1 equiv.) and stirred for 5 min. Added mesyl chloride (0.5 mmol, 0.8 equiv.) dropwise at 0° C. Stirred the reaction mixture at 0° C. for 1 h, reaction temperature was brought to room temperature and stirred overnight. The reaction mixture was diluted with DCM. The DCM layer was washed with 10% NaHCO3 solution followed by water. The DCM layer was collected, dried over Na2SO4, filtered and concentrated. The material obtained was purified by prep HPLC to afford the title compound, N2-(benzo[d]thiazol-6-yl)-N4-isopropyl-5-(5-((1-(methylsulfonyl)piperidin-4-yl)amino)-1,3,4-oxadiazol-2-yl)pyridine-2,4-diamine. 1H NMR: 400 MHz, CD3OD: δ 1.34 (d, J=6.40 Hz, 6H), 1.66-1.75 (m, 2H), 2.10-2.14 (m, 2H), 3.027 (s, 3H), 3.30-3.36 (1H, merged with water peak), 3.56-3.60 (m, 1H), 3.78-3.82 (m, 1H), 4.00-4.05 (m, 2H), 6.17 (s, 1H), 7.53-7.57 (m, 1H), 7.98 (d, J=8.80 Hz, 1H), 8.38 (s, 1H), 8.43 (d, J=2.00 Hz, 1H), 9.08 (s, 1H). LC/MS: ZORBAX SB C18, 4.6×50 mm, 5 μm; Solvent A=10% MeOH: 90% H2O: 0.1% TFA; Solvent B=90% MeOH: 10% H2O: 0.1% TFA; gradient 0-100% B over 2 min (3 min run time); retention time: 1.501 min; LCMS (ES-API), m/z 529.2 (M+H). HPLC: Sunfire C18 (150×4.6 mm), 3.5 micron; Solvent A=5% ACN: 95% H2O: 0.05% TFA pH=2.5; Solvent B=95% ACN: 5% H2O: 0.05% TFA pH=2.5; gradient 0-100% B over 15 min (23 min run time); Flow rate: 1.0 μL/min; Retention time: 5.771 min; Purity: 99.7%.

Aufarbeitung

  1. customdropwise at 0° C
  2. stirringStirred the reaction mixture at 0° C. for 1 h
  3. customreaction temperature
  4. customwas brought to room temperature
  5. stirringstirred overnight
  6. washThe DCM layer was washed with 10% NaHCO3 solution
  7. customThe DCM layer was collected
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe material obtained
  12. customwas purified by prep HPLC

Quellen und Nachweise

ORD-Eintrag
ord-9bac7816c24248409872c6f73d069569
Quelldatensatz
uspto-grants-2016_01
Patentnummer
US09242976B2

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