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Trifluoroacetic acid → 1-{5-tert-butyl-2-[3-(3-hydroxy-propylamino)-phenyl]-2H-pyrazol-3-yl}-3-[4-(pyridin-4-yloxy)-phenyl]-urea

HRID 221899
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 221899
[C:1]([C:5]1[CH:6]=[C:7]([NH:28][C:29]([NH:31][C:32]2[CH:37]=[CH:36][C:35]([O:38][C:39]3[CH:44]=[CH:43][N:42]=[CH:41][CH:40]=3)=[CH:34][CH:33]=2)=[O:30])[N:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([NH:16][CH2:17][CH2:18][CH2:19][O:20][Si](C(C)(C)C)(C)C)[CH:11]=2)[N:9]=1)([CH3:4])([CH3:3])[CH3:2].C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+]>CO.O.C(Cl)Cl>[C:1]([C:5]1[CH:6]=[C:7]([NH:28][C:29]([NH:31][C:32]2[CH:33]=[CH:34][C:35]([O:38][C:39]3[CH:40]=[CH:41][N:42]=[CH:43][CH:44]=3)=[CH:36][CH:37]=2)=[O:30])[N:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([NH:16][CH2:17][CH2:18][CH2:19][OH:20])[CH:11]=2)[N:9]=1)([CH3:4])([CH3:2])[CH3:3]
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Komponenten

7

Edukt 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 536301951-(5-tert-butyl-2-{3-[3-(tert-butyl-dimethyl-silanyloxy)-propylamino]-phenyl}-2H-pyrazol-3-yl)-3-[4-(pyridin-4-yloxy)-phenyl]-urea

Produkt 1

HCID 115696011-{5-tert-butyl-2-[3-(3-hydroxy-propylamino)-phenyl]-2H-pyrazol-3-yl}-3-[4-(pyridin-4-yloxy)-phenyl]-ureaAusbeute 86,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittelHCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of 1-(5-tert-butyl-2-{3-[3-(tert-butyl-dimethyl-silanyloxy)-propylamino]-phenyl}-2H-pyrazol-3-yl)-3-[4-(pyridin-4-yloxy)-phenyl]-urea (117 mg, 0.19 mmol) in methanol (2 mL) was added a solution of 10% TFA in H2O (2 mL). The reaction was stirred at room temperature overnight. The mixture was then diluted with DCM, basified by the addition of saturated aq NaHCO3 and extracted with DCM. The combined organic phases were washed with brine, dried over MgSO4, and concentrated at reduced pressure. The crude residue was purified by MPLC (eluting with 4% to 5.5% MeOH in DCM) to give 82 mg (86%) of the desired product 1-{5-tert-butyl-2-[3-(3-hydroxy-propylamino)-phenyl]-2H-pyrazol-3-yl}-3-[4-(pyridin-4-yloxy)-phenyl]-urea. 1H-NMR (DMSO-d6) δ 9.18 (s, 1H), 8.40 (dd, J=1.7 & 4.7 Hz, 2H), 8.32 (s, 1H), 7.48 (d, J=9.0 Hz, 2H), 7.17 (t, J=7.9 Hz, 1H), 7.07 (d, J=9.1 Hz, 2H), 6.85 (dd, J=1.5 & 4.7 Hz, 2H), 6.63-6.56 (m, 3H), 6.33 (s, 1H), 5.91 (t, J=5.3 Hz, 1H), 4.47 (t, J=5.1 Hz, 1H), 3.48 (q, J=6.1 Hz, 2H), 3.06 (q, J=6.6 Hz, 2H), 1.69 (quintet, J=6.5 Hz, 2H), 1.26 (s, 9H); MS LC-MS [M+H]+=501.2, RT=2.29 min.

Aufarbeitung

  1. extractionextracted with DCM
  2. washThe combined organic phases were washed with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated at reduced pressure
  5. customThe crude residue was purified by MPLC (eluting with 4% to 5.5% MeOH in DCM)

Quellen und Nachweise

ORD-Eintrag
ord-b98eb7c3a5e24990bd97cdf51f8340a0
Quelldatensatz
uspto-grants-2012_06
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08207166B2

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