Acetic Acid → N-({3-[(3-{[(5-Chloro-2-thienyl)sulfonyl]amino}-4-hydroxy-1H-indazol-1-yl)methyl]phenyl}methyl)acetamide

HRID 1808616Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1808616
N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.F[P-](F)(F)(F)(F)F.[C:25]([OH:28])(=O)[CH3:26].C(N(CC)C(C)C)(C)C.C(O)=O.[NH2:41][CH2:42][C:43]1[CH:44]=[C:45]([CH2:49][N:50]2[C:58]3[C:53](=[C:54]([OH:59])[CH:55]=[CH:56][CH:57]=3)[C:52]([NH:60][S:61]([C:64]3[S:65][C:66]([Cl:69])=[CH:67][CH:68]=3)(=[O:63])=[O:62])=[N:51]2)[CH:46]=[CH:47][CH:48]=1>CN(C=O)C>[Cl:69][C:66]1[S:65][C:64]([S:61]([NH:60][C:52]2[C:53]3[C:58](=[CH:57][CH:56]=[CH:55][C:54]=3[OH:59])[N:50]([CH2:49][C:45]3[CH:44]=[C:43]([CH2:42][NH:41][C:25](=[O:28])[CH3:26])[CH:48]=[CH:47][CH:46]=3)[N:51]=2)(=[O:62])=[O:63])=[CH:68][CH:67]=1

Komponenten

6

Edukt 4

HCID 176Acetic AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 136346357n-(1-{[3-(Aminomethyl)phenyl]methyl}-4-hydroxy-1h-indazol-3-yl)-5-chloro-2-thiophenesulfonamide formate salt

Produkt 1

HCID 136116031N-({3-[(3-{[(5-Chloro-2-thienyl)sulfonyl]amino}-4-hydroxy-1H-indazol-1-yl)methyl]phenyl}methyl)acetamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

To a solution of O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium-hexafluorophosphate (39.7 mg, 0.064 mmol) in anhydrous DMF (1 mL) was added at room temperature acetic acid (3.36 μL, 0.059 mmol), followed by N,N-diisopropylethylamine (0.031 mL, 0.18 mmol) and finally a solution of N-(1-{[3-(aminomethyl)phenyl]methyl}-4-hydroxy-1H-indazol-3-yl)-5-chloro-2-thiophenesulfonamide formate salt (for a preparation see Intermediate 15) (29 mg, 0.059 mmol) in anhydrous DMF (1 mL) and the reaction mixture was stirred at room temperature for 30 min. The mixture was partitioned between saturated aqueous sodium hydrogen carbonate solution and ethyl acetate. The organic layer was separated, washed with brine:water (1:1), passed through a hydrophobic frit and evaporated in-vacuo to yield a colourless oil (23 mg). This was dissolved in MeOH:DMSO (1 mL) and purified by MDAP Sunfire C18 column eluting with solvents A/B (A: 0.1% v/v solution of formic acid in water, B: 0.1% v/v solution of formic acid in acetonitrile) (25 min run). The appropriate fraction was evaporated in-vacuo to yield the title compound as a colourless oil (20 mg, 69%). LCMS (System B) RT=2.41 min, ES+ve m/z 491/493 (M+H)+.

Aufarbeitung

  1. customThe mixture was partitioned between saturated aqueous sodium hydrogen carbonate solution and ethyl acetate
  2. customThe organic layer was separated
  3. washwashed with brine:water (1:1)
  4. customevaporated in-vacuo

Quellen und Nachweise

ORD-Eintrag
ord-a86f365d665848a299fc234d74006382
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08357716B2

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