Hydrochloric Acid → 2'-tert-butyl-1-(7-m ethoxy-1H-indazole-5-carbonyl)-4',6'-dihydrospiro[piperidine-4,5'-pyrazolo[3,4-c]pyridin]-7'(2'H)-one

HRID 537195Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 537195
Cl.[C:2]([N:6]1[CH:14]=[C:13]2[C:8]([C:9](=[O:20])[NH:10][C:11]3([CH2:19][CH2:18][NH:17][CH2:16][CH2:15]3)[CH2:12]2)=[N:7]1)([CH3:5])([CH3:4])[CH3:3].[CH3:21][O:22][C:23]1[CH:24]=[C:25]([C:38](O)=[O:39])[CH:26]=[C:27]2[C:31]=1[N:30](C1CCCCO1)[N:29]=[CH:28]2.C(N(CC)CC)C.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O.Cl>CN(C)C=O.O>[C:2]([N:6]1[CH:14]=[C:13]2[C:8]([C:9](=[O:20])[NH:10][C:11]3([CH2:19][CH2:18][N:17]([C:38]([C:25]4[CH:26]=[C:27]5[C:31](=[C:23]([O:22][CH3:21])[CH:24]=4)[NH:30][N:29]=[CH:28]5)=[O:39])[CH2:16][CH2:15]3)[CH2:12]2)=[N:7]1)([CH3:5])([CH3:3])[CH3:4]

Komponenten

8

Edukt 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 111923Propylphosphonic anhydrideHCID 674913562'-(tert-Butyl)-4',6'-dihydrospiro[piperidine-4,5'-pyrazolo[3,4-c]pyridin]-7'(2'H)-one hydrochloride2×HCID 674914847-methoxy-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxylic acid2×

Produkt 1

HCID 674916982'-tert-butyl-1-(7-m ethoxy-1H-indazole-5-carbonyl)-4',6'-dihydrospiro[piperidine-4,5'-pyrazolo[3,4-c]pyridin]-7'(2'H)-oneAusbeute 10,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a mixture of 2′-tert-butyl-4′,6′-dihydrospiro[piperidine-4,5′-pyrazolo[3,4-c]pyridin]-7′(2′H)-one hydrochloride salt (Intermediate 4, 25 mg, 0.075 mmol) and 7-methoxy-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxylic acid (Intermediate 18, 25 mg, 0.090 mmol) in N,N-dimethylformamide (0.4 mL) was added triethylamine (0.05 mL, 0.37 mmol). The mixture was stirred for 5 minutes. Then 1-propanephosphonic acid cyclic anhydride (0.09 mL, 0.1 mmol, 50% solution in ethyl acetate) was added and the reaction was stirred at room temperature overnight. The reaction was diluted with water and extracted with ethyl acetate (3 x). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated to a yellow gum. To this crude material was added hydrochloric acid (0.19 mL, 0.75 mmol, 4 M in dioxane). The mixture was stirred at room temperature overnight. The reaction was concentrated. Purification by reversed-phase HPLC gave the title compound (3.4 mg, 10%). +ESI (M+H) 437.3; HPLC retention time 2.12 minutes (Method A).

Aufarbeitung

  1. stirringthe reaction was stirred at room temperature overnight
  2. extractionextracted with ethyl acetate (3 x)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to a yellow gum
  7. stirringThe mixture was stirred at room temperature overnight
  8. concentrationThe reaction was concentrated
  9. customPurification by reversed-phase HPLC

Quellen und Nachweise

ORD-Eintrag
ord-4c767c7945f24126b3fc385ddfb58b0f
Quelldatensatz
uspto-grants-2014_10
Patentnummer
US08859773B2

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