Water → tert-butyl 2-(3-carbamoyl-1H-pyrazolo[3,4-c]pyridin-1-yl)acetate

HRID 1527290Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1527290
I[C:2]1[C:10]2[C:5](=[CH:6][N:7]=[CH:8][CH:9]=2)[N:4]([CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[N:3]=1.O.C[N:21]([CH:23]=[O:24])C>CCOC(C)=O.[C-]#N.[C-]#N.[Zn+2].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:23]([C:2]1[C:10]2[C:5](=[CH:6][N:7]=[CH:8][CH:9]=2)[N:4]([CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[N:3]=1)(=[O:24])[NH2:21]

Komponenten

8

Edukt 3

HCID 962WaterHCID 6228DimethylformamideHCID 68283649Tert-butyl 2-(3-iodo-1H-pyrazolo[3,4-c]pyridin-1-yl)acetate

Produkt 1

HCID 68284362tert-butyl 2-(3-carbamoyl-1H-pyrazolo[3,4-c]pyridin-1-yl)acetate

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 11186Zinc cyanide (Zn(CN)2)KatalysatorHCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of tert-butyl 2-(3-iodo-1H-pyrazolo[3,4-c]pyridin-1-yl)acetate (3.76 g, 10.5 mmol), Zn(CN)2 (1.35 g, 11.5 mmol), Pd(dppf)Cl2 (855 mg, 1.05 mmol), Pd2(dba)3 (959 mg, 1.05 mmol), water (4 mL) and DMF (30 mL) was stirred at 100° C. for 16 h under argon. The reaction mixture was diluted with EtOAc and then was successively washed with water, sat. aq. NaHCO3 (2×) and brine, dried (Phase separator) and concentrated under vacuum. The residual oil was purified by flash column chromatography on silica gel (EtOAc/c-hexane 1:1 then 100% EtOAc). MS (LC/MS): 259.0 [M+H]+; tR (HPLC conditions k): 3.10 min. Further elution of the column with CH2Cl2/MeOH 8:2 and subsequent purification by preparative HPLC (Macherey-Nagel Nucleosil 100-10 C18, 5 μm, 40×250 mm, flow: 40 mL/min, eluent: 5-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA) afforded tert-butyl 2-(3-carbamoyl-1H-pyrazolo[3,4-c]pyridin-1-yl)acetate as a side-product. MS (LC/MS): 277.0 [M+H]+; tR (HPLC conditions k): 2.39 min.

Aufarbeitung

  1. washwas successively washed with water, sat. aq. NaHCO3 (2×) and brine
  2. customdried (Phase separator)
  3. concentrationconcentrated under vacuum
  4. customThe residual oil was purified by flash column chromatography on silica gel (EtOAc/c-hexane 1:1
  5. custom3.10 min
  6. washFurther elution of the column
  7. customwith CH2Cl2/MeOH 8:2 and subsequent purification by preparative HPLC (Macherey-Nagel Nucleosil 100-10 C18, 5 μm, 40×250 mm, flow: 40 mL/min, eluent: 5-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA)

Quellen und Nachweise

ORD-Eintrag
ord-649446bef7904659a60907c55b9d8437
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09085555B2

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