Potassium Phosphate, Tribasic → 2-(5-chloro-indazol-1-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide

HRID 245970Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 245970
[O-]P([O-])([O-])=O.[K+].[K+].[K+].[Cl:9][C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][CH:18]=1)[NH:15][N:14]=[CH:13]2.[C:19]([CH:21]1[CH2:24][N:23]([C:25](=[O:49])[C@H:26]([NH:28][C:29]([C:31]2[C:39]3[C:34](=[N:35][CH:36]=[C:37](I)[N:38]=3)[N:33]([CH2:41][O:42][CH2:43][CH2:44][Si:45]([CH3:48])([CH3:47])[CH3:46])[CH:32]=2)=[O:30])[CH3:27])[CH2:22]1)#[N:20].CN[C@@H]1CCCC[C@H]1NC>[Cu]I.C1(C)C=CC=CC=1>[C:19]([CH:21]1[CH2:22][N:23]([C:25](=[O:49])[C@H:26]([NH:28][C:29]([C:31]2[C:39]3[C:34](=[N:35][CH:36]=[C:37]([N:15]4[C:16]5[C:12](=[CH:11][C:10]([Cl:9])=[CH:18][CH:17]=5)[CH:13]=[N:14]4)[N:38]=3)[N:33]([CH2:41][O:42][CH2:43][CH2:44][Si:45]([CH3:48])([CH3:47])[CH3:46])[CH:32]=2)=[O:30])[CH3:27])[CH2:24]1)#[N:20]

Komponenten

7

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 696811H-Indazole, 5-chloro-HCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 866779282-iodo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide

Produkt 1

HCID 712888852-(5-chloro-indazol-1-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amideAusbeute 58 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

In a 5 mL microwave vial were placed copper(I) iodide (6 mg, 0.033 mmol), K3PO4 (132 mg, 0.62 mmol), 5-chloro-1H-indazole (54 mg, 0.36 mmol), 2-iodo-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide (164 mg, 0.30 mmol), toluene (1.2 mL), and trans-N,N′-dimethylcyclohexane-1,2-diamine (9 mg, 0.066 mmol). The vial was purged with a stream of nitrogen then sealed and heated in an oil bath at 110° C. for 24 h. The reaction mixture was cooled to room temperature and diluted with EtOAc then filtered over a Buchner funnel, rinsing with EtOAc. The filtrate was concentrated and the resultant residue was purified by silica gel chromatography with 50% to 80% EtOAc/hexanes to afford 100 mg (58%) of 2-(5-chloro-indazol-1-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide as a light yellow foam.

Aufarbeitung

  1. customThe vial was purged with a stream of nitrogen
  2. customthen sealed
  3. temperatureThe reaction mixture was cooled to room temperature
  4. additiondiluted with EtOAc
  5. filtrationthen filtered over a Buchner funnel
  6. washrinsing with EtOAc
  7. concentrationThe filtrate was concentrated
  8. customthe resultant residue was purified by silica gel chromatography with 50% to 80% EtOAc/hexanes

Quellen und Nachweise

ORD-Eintrag
ord-f2c21ff60420412b998e6eae71eed592
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658646B2

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