Tetrabutylammonium Fluoride → 1-[5-tert-Butyl-2-(2-hydroxy-ethyl)-2H-pyrazol-3-yl]-3-[(1S,4R)-4-(3-isopropyl[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea

HRID 75583Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 75583
[C:1]([C:5]1[CH:6]=[C:7]([NH:20][C:21]([NH:23][C@@H:24]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[C@H:27]([O:34][C:35]3[CH:36]=[CH:37][C:38]4[N:39]([C:41]([CH:44]([CH3:46])[CH3:45])=[N:42][N:43]=4)[CH:40]=3)[CH2:26][CH2:25]2)=[O:22])[N:8]([CH2:10][CH2:11][O:12][Si](C(C)(C)C)(C)C)[N:9]=1)([CH3:4])([CH3:3])[CH3:2].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.O.C(Cl)Cl>[C:1]([C:5]1[CH:6]=[C:7]([NH:20][C:21]([NH:23][C@@H:24]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[C@H:27]([O:34][C:35]3[CH:36]=[CH:37][C:38]4[N:39]([C:41]([CH:44]([CH3:46])[CH3:45])=[N:42][N:43]=4)[CH:40]=3)[CH2:26][CH2:25]2)=[O:22])[N:8]([CH2:10][CH2:11][OH:12])[N:9]=1)([CH3:4])([CH3:3])[CH3:2]

Komponenten

6

Edukt 2

HCID 2724141Tetrabutylammonium FluorideHCID 86686687HCID 86686687, Verbindung

Produkt 1

HCID 715998751-[5-tert-Butyl-2-(2-hydroxy-ethyl)-2H-pyrazol-3-yl]-3-[(1S,4R)-4-(3-isopropyl[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-ureaAusbeute 58,9 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of Intermediate 10d (100 mg, 0.15 mmol) in THF (2 mL), TBAF (1M in THF, 0.23 mL, 0.23 mmol) was added at RT and stirred for 10 min. The reaction mixture was diluted with H2O (5 mL) and DCM (5 mL). The layers were separated, and aqueous layer was extracted with DCM (3×5 mL). The combined organic layers were dried (MgSO4), filtered, concentrated in vacuo and then purified by FCC using 0-5% [2M NH3 in MeOH] in DCM). The residue was washed with water and purified by HPLC (30%-100% MeCN in H2O, 0.1% formic acid) to give the title compound as a white powder (47 mg, 57%). Rf=0.2 (5% [2M NH3 in MeOH] in DCM) LCMS (Method 5): Rt 3.59 min, m/z 532 [MH+]. 1H NMR (400 MHz, CDCl3): 1H NMR (300 MHz, CDCl3): 1.25 (s, 9H), 1.43 (d, J=6.9 Hz, 3H), 1.46 (d, J=6.9 Hz, 3H), 1.92-2.30 (m, 4H), 3.25 (p, J=6.9 Hz, 1H), 3.95 (t, J=4.7 Hz, 2H), 4.15 (dd, J=5.3, 3.5 Hz, 2H), 5.09-5.16 (m, 1H), 5.92 (d, J=8.0 Hz, 1H), 6.12 (s, 1H), 6.92 (dd, J=9.8, 1.9 Hz, 1H), 7.22-7.27 (m, 2H), 7.33 (td, J=5.8, 3.0 Hz, 1H), 7.40 (s, 1H), 7.43 (br s, 2H), 7.47 (d, J=7.8 Hz, 1H), 7.70 (s, 1H).

Aufarbeitung

  1. customThe layers were separated
  2. extractionaqueous layer was extracted with DCM (3×5 mL)
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. custompurified by FCC
  7. washThe residue was washed with water
  8. custompurified by HPLC (30%-100% MeCN in H2O, 0.1% formic acid)

Quellen und Nachweise

ORD-Eintrag
ord-143822b55ffe417cb3d8b95bb47139f3
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08835431B2

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