1-Methyl-3-tributylstannanyl-1,4,5,6,7,8-hexahydrocycloheptapyrazole → 2-(1-methyl-1,4,5,6,7,8-hexahydrocycloheptapyrazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide

HRID 246335

Reaktionsgleichung

Reaktionsgleichung von HRID 246335
[CH3:1][N:2]1[C:6]2[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][C:5]=2[C:4]([Sn](CCCC)(CCCC)CCCC)=[N:3]1.[C:25]([NH:29][C:30]([C:32]1[C:40]2[C:35](=[N:36][CH:37]=[C:38](Br)[N:39]=2)[N:34]([CH2:42][O:43][CH2:44][CH2:45][Si:46]([CH3:49])([CH3:48])[CH3:47])[CH:33]=1)=[O:31])([CH3:28])([CH3:27])[CH3:26]>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[C:25]([NH:29][C:30]([C:32]1[C:40]2[C:35](=[N:36][CH:37]=[C:38]([C:4]3[C:5]4[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][C:6]=4[N:2]([CH3:1])[N:3]=3)[N:39]=2)[N:34]([CH2:42][O:43][CH2:44][CH2:45][Si:46]([CH3:49])([CH3:48])[CH3:47])[CH:33]=1)=[O:31])([CH3:28])([CH3:27])[CH3:26]

Komponenten

6

Edukt 2

HCID 712802921-Methyl-3-tributylstannanyl-1,4,5,6,7,8-hexahydrocycloheptapyrazoleHCID 715756452-bromo-N-(tert-butyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Produkt 1

HCID 712794412-(1-methyl-1,4,5,6,7,8-hexahydrocycloheptapyrazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamideAusbeute 60,4 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418397HCID 178418397, VerbindungKatalysatorHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a solution of 1-methyl-3-tributylstannyl-1,4,5,6,7,8-hexahydrocycloheptapyrazole (74 mg, 0.17 mmol) and 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (60 mg, 0.14 mmol) in DMF (2 mL) were added Pd(PPh3)4 (8 mg, 0.007 mmol) and copper(I) iodide (5 mg, 0.028 mmol). The reaction mixture was heated at 80° C. for 1.5 h then cooled to room temperature, quenched with water and extracted with EtOAc (2×). The combined organics were washed with water (3×) and brine then dried over MgSO4 and concentrated. The residue was absorbed on SiO2 and chromatographed with 20% to 50% EtOAc/hexanes to isolate 42 mg (60%) of 2-(1-methyl-1,4,5,6,7,8-hexahydrocycloheptapyrazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide as a pale orange-yellow solid.

Aufarbeitung

  1. temperaturethen cooled to room temperature
  2. customquenched with water
  3. extractionextracted with EtOAc (2×)
  4. washThe combined organics were washed with water (3×) and brine
  5. dry with materialthen dried over MgSO4
  6. concentrationconcentrated
  7. customThe residue was absorbed on SiO2
  8. customchromatographed with 20% to 50% EtOAc/hexanes

Quellen und Nachweise

ORD-Eintrag
ord-358e0ad696c84202a5e1371358c80a73
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658646B2

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