6-chloro-1-methyl-3-tributylstannanyl-1H-indazole → tert-butyl 3-(2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)cyclohexylcarbamate

HRID 246705Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 246705
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([Sn](CCCC)(CCCC)CCCC)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1.Br[C:26]1[N:27]=[C:28]2[C:34]([C:35]([NH:37][CH:38]3[CH2:43][CH2:42][CH2:41][CH:40]([NH:44][C:45](=[O:51])[O:46][C:47]([CH3:50])([CH3:49])[CH3:48])[CH2:39]3)=[O:36])=[CH:33][NH:32][C:29]2=[N:30][CH:31]=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>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:26]3[N:27]=[C:28]4[C:34]([C:35]([NH:37][CH:38]5[CH2:43][CH2:42][CH2:41][CH:40]([NH:44][C:45](=[O:51])[O:46][C:47]([CH3:49])([CH3:48])[CH3:50])[CH2:39]5)=[O:36])=[CH:33][NH:32][C:29]4=[N:30][CH:31]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1

Komponenten

6

Edukt 2

HCID 712805996-chloro-1-methyl-3-tributylstannanyl-1H-indazoleHCID 86678006tert-butyl 3-(2-bromo-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)cyclohexylcarbamate

Produkt 1

HCID 71279706tert-butyl 3-(2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)cyclohexylcarbamateAusbeute 56 %

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

A mixture of 6-chloro-1-methyl-3-(tributylstannyl)-1H-indazole (0.47 g, 1.03 mmol), tert-butyl 3-(2-bromo-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)cyclohexylcarbamate (0.45 g, 1.03 mmol), CuI (0.07 g, 0.37 mmol) and Pd(PPh3)4 (0.07 g, 0.06 mmol) in 100 mL of DMF was stirred at 80° C. under nitrogen atmosphere overnight. The solvent was removed under reduced pressure and the residue was purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 mL/inj, flow rate: 20 mL/min; wavelength: 214 nm and 254 nm; the gradient conditions were: 50% acetonitrile/50% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 85% acetonitrile/15% water (0.1% trifluoroacetic acid, v/v) in a linear fashion over 9 min.) to give tert-butyl 3-(2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)cyclohexylcarbamate (0.3 g, 56%) as a yellow solid. MS: (M+H)+=542.2; 1H NMR (300 MHz, DMSO): δ 9.13-9.07 (m, 1H), 8.48-8.39 (m, 2H), 8.13-8.01 (m, 2H), 7.42-7.30 (m, 1H), 5.20 (s, 3H), 3.44-3.35 (m, 1H), 2.30-2.05 (m, 1H), 1.82-1.38 (m, 4H), 1.32-1.17 (m, 13H).

Aufarbeitung

  1. customThe solvent was removed under reduced pressure
  2. customthe residue was purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm
  3. wait50% acetonitrile/50% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 85% acetonitrile/15% water (0.1% trifluoroacetic acid, v/v) in a linear fashion over 9 min.

Quellen und Nachweise

ORD-Eintrag
ord-2ed654572ec04253b75bb7183d51f69a
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658646B2

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