18-Crown-6 → tert-butyl 4-{1-(2-tetrahydropyranyl)-1H-indazol-5-ylamino}benzoate

HRID 1269892

Reaktionsgleichung

Reaktionsgleichung von HRID 1269892
Br[C:2]1[CH:14]=[CH:13][C:5]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])=[CH:4][CH:3]=1.C1OCCOCCOCCOCCOCCOC1.[O:33]1[CH2:38][CH2:37][CH2:36][CH2:35][CH:34]1[N:39]1[C:47]2[C:42](=[CH:43][C:44]([NH2:48])=[CH:45][CH:46]=2)[CH:41]=[N:40]1.C(NC1C(C)=CC(C(OC)=O)=C(C)C=1)(=O)C.CC(C)([O-])C.[Na+].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C(OCC)C.C1(C)C=CC=CC=1>[O:33]1[CH2:38][CH2:37][CH2:36][CH2:35][CH:34]1[N:39]1[C:47]2[C:42](=[CH:43][C:44]([NH:48][C:2]3[CH:14]=[CH:13][C:5]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])=[CH:4][CH:3]=3)=[CH:45][CH:46]=2)[CH:41]=[N:40]1

Komponenten

9

Edukt 6

HCID 2855718-Crown-6HCID 327521Methyl 4-acetamido-2,5-dimethylbenzoateHCID 634876Binap, (A+-)-HCID 11334366Tert-butyl 4-bromobenzoateHCID 229339271-(Oxan-2-yl)-1H-indazol-5-amineHCID 23676156Sodium t-butoxide

Produkt 1

HCID 69433104tert-butyl 4-{1-(2-tetrahydropyranyl)-1H-indazol-5-ylamino}benzoateAusbeute 56 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 1140TolueneLösungsmittelHCID 3283Diethyl EtherLösungsmittel

Versuchsvorschrift

In a two-necked flask the inner atmosphere of which had been replaced with nitrogen were placed tert-butyl 4-bromobenzoate (2.57 mg, 1.00 mmol), toluene (2 ml), 18-crown-6 (380 mg, 1.40 mmol), the 1-(2-tetrahydropyranyl)-1H-indazol-5-amine (261 mg, 1.23 mmol) obtained in Example 317, (e) and sodium tert-butoxide (135 mg, 1.40 mmol) in that order. After the inner atmosphere of the flask was replaced with nitrogen again, tris(dibenzylideneacetone)(chloroform) dipalladium(0) (52 mg, 0.050 mmol) and (S)-2,2′-bis(diphenylphophino)-1,1′-binaphthyl (94 mg, 0.151 mmol) were added. After the third replacement of the inner atmosphere of the flask with nitrogen, stirring was conducted at 80° C. for 8 hours. The resulting mixture was diluted with diethyl ether and the solid was removed by filtration using Celite. Then, the solvent was distilled off under reduced pressure to obtain a crude product. The crude product was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate=3/1) to obtain tert-butyl 4-{1-(2-tetrahydropyranyl)-1H-indazol-5-ylamino}benzoate (218 mg, 56%).

Aufarbeitung

  1. customIn a two-necked flask the inner atmosphere of which had been replaced with nitrogen
  2. customthe solid was removed by filtration
  3. distillationThen, the solvent was distilled off under reduced pressure
  4. customto obtain a crude product
  5. customThe crude product was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate=3/1)

Quellen und Nachweise

ORD-Eintrag
ord-7171331d452549a1932e5a6d8ccbf5ae
Quelldatensatz
uspto-grants-2007_04
Patentnummer
US07199147B2

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