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1,4-Dioxane → N-[1-{[3-(Aminomethyl)phenyl]methyl}-4-(1-hydroxy-1-methylethyl)-1H-indazol-3-yl]-5-chloro-2-thiophenesulfonamide

HRID 1874702
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1874702
C[Mg]Br.CC([N:8]([CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([CH2:19][N:20]2[C:28]3[C:23](=[C:24]([C:29](=[O:31])[CH3:30])[CH:25]=[CH:26][CH:27]=3)[C:22]([NH:32][S:33]([C:36]3[S:37][C:38]([Cl:41])=[CH:39][CH:40]=3)(=[O:35])=[O:34])=[N:21]2)[CH:14]=1)C(=O)[O-])(C)C.O1CCOC[CH2:43]1>C1COCC1.Cl>[NH2:8][CH2:12][C:13]1[CH:14]=[C:15]([CH2:19][N:20]2[C:28]3[C:23](=[C:24]([C:29]([OH:31])([CH3:30])[CH3:43])[CH:25]=[CH:26][CH:27]=3)[C:22]([NH:32][S:33]([C:36]3[S:37][C:38]([Cl:41])=[CH:39][CH:40]=3)(=[O:35])=[O:34])=[N:21]2)[CH:16]=[CH:17][CH:18]=1
KomponentenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

6

Edukt 3

HCID 312751,4-DioxaneHCID 866448151,1-dimethylethyl({3-[(4-acetyl-3-{[(5-chloro-2-thienyl)sulfonyl]amino}-1H-indazol-1-yl)methyl]phenyl}methyl)carbamateHCID 178418573HCID 178418573, Verbindung2×

Produkt 1

HCID 59456043N-[1-{[3-(Aminomethyl)phenyl]methyl}-4-(1-hydroxy-1-methylethyl)-1H-indazol-3-yl]-5-chloro-2-thiophenesulfonamideAusbeute 76 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 313Hydrochloric AcidLösungsmittel2×HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

Methylmagnesium bromide (3M solution in diethyl ether) (0.730 mL, 2.191 mmol) was added slowly dropwise to a stirring solution of 1,1-dimethylethyl({3-[(4-acetyl-3-{[(5-chloro-2-thienyl)sulfonyl]amino}-1H-indazol-1-yl)methyl]phenyl}methyl)carbamate (for a preparation see Intermediate 76) (210 mg, 0.365 mmol) in THF (3 mL) at room temp. The reaction was stirred for 2 h and then more methylmagnesium bromide (3M solution in diethyl ether) (0.730 mL, 2.191 mmol) was added and stirred overnight. LCMS indicated molecular ion 592 [M+1] corresponding to the desired alcohol and that the starting material co-eluted with the product. 1N HCl (5 mL) was added and the product was extracted with EtOAc (15 mL×3). The combined organic layers were dried by passing through a hydrophobic frit and concentrated in vacuo. The residue was dissolved in 4N HCl in Dioxane (2 mL, 8.00 mmol) and the reaction was stirred at room temp over 1 h. The reaction mixture was loaded on an SCX-2 ion-exchange 20 g cartridge eluting with methanol and 2M ammonia in methanol. The appropriate ammoniacal fractions were combined and evaporated in vacuo to give the title compound (168 mg, 76%) as a brown oil. LCMS (System A) RT=0.79 min, ES+ve m/z 491/493 (M+H)+.

Aufarbeitung

  1. customat room temp
  2. stirringstirred overnight
  3. extractionthe product was extracted with EtOAc (15 mL×3)
  4. customThe combined organic layers were dried
  5. concentrationconcentrated in vacuo
  6. stirringthe reaction was stirred at room temp over 1 h
  7. washeluting with methanol and 2M ammonia in methanol
  8. customevaporated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-6505e2e62ef34c8b8d5e03cd11eb51d7
Quelldatensatz
uspto-grants-2012_11
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08304446B2

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