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Acetohydroxamic Acid → 1-(3-amino-1,2-benzisoxazol-5-yl)-6-[4-(2-oxo-1-piperidinyl)phenyl]-3-(trifluoromethyl)-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridine-7-one

HRID 1391925
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1391925
C([NH:4][OH:5])(=O)C.C([O-])([O-])=O.[K+].[K+].F[C:13]1[CH:20]=[CH:19][C:18]([N:21]2[C:25]3[C:26](=[O:43])[N:27]([C:30]4[CH:35]=[CH:34][C:33]([N:36]5[CH2:41][CH2:40][CH2:39][CH2:38][C:37]5=[O:42])=[CH:32][CH:31]=4)[CH2:28][CH2:29][C:24]=3[C:23]([C:44]([F:47])([F:46])[F:45])=[N:22]2)=[CH:17][C:14]=1[C:15]#[N:16].C(O)(C(F)(F)F)=O>CN(C=O)C.O>[NH2:16][C:15]1[C:14]2[CH:17]=[C:18]([N:21]3[C:25]4[C:26](=[O:43])[N:27]([C:30]5[CH:35]=[CH:34][C:33]([N:36]6[CH2:41][CH2:40][CH2:39][CH2:38][C:37]6=[O:42])=[CH:32][CH:31]=5)[CH2:28][CH2:29][C:24]=4[C:23]([C:44]([F:46])([F:45])[F:47])=[N:22]3)[CH:19]=[CH:20][C:13]=2[O:5][N:4]=1
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Komponenten

7

Edukt 4

HCID 1990Acetohydroxamic AcidHCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 222500932-fluoro-5-[7-oxo-6-[4-(2-oxo-1-piperidinyl)phenyl]-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridin-1-yl]benzonitrile

Produkt 1

HCID 10185866
1-(3-amino-1,2-benzisoxazol-5-yl)-6-[4-(2-oxo-1-piperidinyl)phenyl]-3-(trifluoromethyl)-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridine-7-one
Ausbeute 81,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

Acetohydroxamic acid (54 mg, 0.72 mmol) and K2CO3 (0.2 g, 1.45 mmol) were added to 8 mL of DMF and 4 mL of H2O. The mixture was stirred at rt for 15 min, followed by addition of a solution of 2-fluoro-5-[7-oxo-6-[4-(2-oxo-1-piperidinyl)phenyl]-3-(trifluoromethyl)-4,5,6,7,-tetrahydro-1H-pyrazolo[3,4-c]pyridin-1-yl]benzonitrile (0.12 g, 0.24 mmol) in DMF(2 mL). The mixture was stirred at rt overnight. The mixture was then partitioned between ethylacetate (40 mL) and water (20 mL), washed with H20 (20 mL×3) and brine (20 mL), dried over Na2SO4, filtered, and concentrated. HPLC (C18 RP., 0.5% TFA, H2O/MeCN gradient) purification gave 100 mg (67% yield) of the title compound as its TFA salt. LRMS (ESI−): 623.4 (M+TFA−H)−. 1H NMR (CDCl3) δ 7.80 (s, 1H), 7.72 (d, 1H), 7.44 (d, 1H), 7.34-7.24 (m, 4H), 4.16 (t, 2H), 3.98 (br, 2H), 3.61 (br, 2H), 3.20 (t, 2H), 2.60 (br, 2H), 1.98-1.89 (m, 4H).

Aufarbeitung

  1. stirringThe mixture was stirred at rt overnight
  2. customThe mixture was then partitioned between ethylacetate (40 mL) and water (20 mL)
  3. washwashed with H20 (20 mL×3) and brine (20 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customHPLC (C18 RP., 0.5% TFA, H2O/MeCN gradient) purification

Quellen und Nachweise

ORD-Eintrag
ord-39daa9fa7ed94adcb6d91a176b8fb01e
Quelldatensatz
uspto-grants-2008_03
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US07338963B2

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