3-(5-(difluoromethoxy)-3-(tributylstannyl)-1H-indazol-1-yl)-N,N-dimethylpropan-1-amine → N-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-(5-(difluoromethoxy)-1-(3-(dimethylamino)propyl)-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide

HRID 246702Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 246702
[F:1][CH:2]([F:32])[O:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH2:13][CH2:14][CH2:15][N:16]([CH3:18])[CH3:17])[N:8]=[C:7]2[Sn](CCCC)(CCCC)CCCC.Br[C:34]1[N:39]=[C:38]2[C:40]([C:62]([NH:64][C:65]([CH3:76])([CH3:75])[CH2:66][O:67][Si:68]([C:71]([CH3:74])([CH3:73])[CH3:72])([CH3:70])[CH3:69])=[O:63])=[CH:41][N:42]([C:43]([C:56]3[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=3)([C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)[C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)[C:37]2=[N:36][CH:35]=1>CN(C=O)C.[Cu]I.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>[Si:68]([O:67][CH2:66][C:65]([NH:64][C:62]([C:40]1[C:38]2=[N:39][C:34]([C:7]3[C:6]4[C:10](=[CH:11][CH:12]=[C:4]([O:3][CH:2]([F:1])[F:32])[CH:5]=4)[N:9]([CH2:13][CH2:14][CH2:15][N:16]([CH3:17])[CH3:18])[N:8]=3)=[CH:35][N:36]=[C:37]2[N:42]([C:43]([C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=2)([C:56]2[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=2)[C:50]2[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=2)[CH:41]=1)=[O:63])([CH3:75])[CH3:76])([C:71]([CH3:72])([CH3:73])[CH3:74])([CH3:70])[CH3:69]

Komponenten

6

Edukt 2

HCID 712800443-(5-(difluoromethoxy)-3-(tributylstannyl)-1H-indazol-1-yl)-N,N-dimethylpropan-1-amineHCID 866780042-bromo-N-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide

Produkt 1

HCID 71280050N-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-(5-(difluoromethoxy)-1-(3-(dimethylamino)propyl)-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamideAusbeute 46,6 %

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 3-(5-(difluoromethoxy)-3-(tributylstannyl)-1H-indazol-1-yl)-N,N-dimethylpropan-1-amine (120 mg, 0.22 mmol) and 2-bromo-N-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (200 mg, 0.26 mmol) in DMF (10 mL) were added CuI (30 mg, 0.16 mmol) and Pd(PPh3)4 (47 mg, 0.041 mmol), Then the reaction mixture was degassed by bubbling nitrogen for 3 minutes and refilled with nitrogen. The mixture was heated to 80° C. for 5 hours under nitrogen. After cooling to room temperature, water (50 mL) was added and product extracted with EtOAc (3×40 mL), the combined organic layers were dried over Na2SO4, filtered and concentrated to give N-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-(5-(difluoromethoxy)-1-(3-(dimethylamino)propyl)-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (88 mg, crude) as a yellow oil. LCMS: (M+H)+=858.

Aufarbeitung

  1. customthe reaction mixture was degassed
  2. customby bubbling nitrogen for 3 minutes
  3. additionrefilled with nitrogen
  4. temperatureAfter cooling to room temperature
  5. additionwater (50 mL) was added
  6. extractionproduct extracted with EtOAc (3×40 mL)
  7. dry with materialthe combined organic layers were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-167c63012f184e998dea6447886e2db6
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658646B2

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