Sodium Carbonate → 2-[4-Amino-5-(2-benzyl-2H-indazol-6-yl)-pyrrolo[2,1-f][1,2,4]triazin-7-ylmethyl]-cyclopropanecarboxylic acid ethyl ester

HRID 1972877Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1972877
[CH2:1]([O:3][C:4]([CH:6]1[CH2:8][CH:7]1[CH2:9][C:10]1[N:18]2[C:13]([C:14]([NH2:19])=[N:15][CH:16]=[N:17]2)=[C:12](Br)[CH:11]=1)=[O:5])[CH3:2].[CH2:21]([N:28]1[CH:36]=[C:35]2[C:30]([CH:31]=[C:32](B3OC(C)(C)C(C)(C)O3)[CH:33]=[CH:34]2)=[N:29]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C([O-])([O-])=O.[Na+].[Na+]>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>[CH2:1]([O:3][C:4]([CH:6]1[CH2:8][CH:7]1[CH2:9][C:10]1[N:18]2[C:13]([C:14]([NH2:19])=[N:15][CH:16]=[N:17]2)=[C:12]([C:32]2[CH:33]=[CH:34][C:35]3[C:30]([CH:31]=2)=[N:29][N:28]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:36]=3)[CH:11]=1)=[O:5])[CH3:2]

Komponenten

6

Edukt 3

HCID 10340Sodium CarbonateHCID 585293132-benzyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-IndazoleHCID 585297512-(4-Amino-5-bromo-pyrrolo[2,1-f][1,2,4]triazin-7-ylmethyl)-cyclopropanecarboxylic acid ethyl ester

Produkt 1

HCID 585293712-[4-Amino-5-(2-benzyl-2H-indazol-6-yl)-pyrrolo[2,1-f][1,2,4]triazin-7-ylmethyl]-cyclopropanecarboxylic acid ethyl esterAusbeute 54 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of 2-(4-amino-5-bromo-pyrrolo[2,1-f][1,2,4]triazin-7-ylmethyl)-cyclopropanecarboxylic acid ethyl ester (1.33 g, 4 mmol) in degassed DMF (6.6 mL) was added 2-benzyl-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-2H-indazole (2.1 g, 6.3 mmol), Pd(PPh3)4, and 2N Na2CO3 solution (5.3 mL). The reaction was irradiated in a microwave reactor at 150° C. for 10 min. After cooling the mixture was partitioned between EtOAc and H2O. The organic phase was separated and dried over Na2SO4, filtered, and evaporated in vacuo. The crude was purified by Biotage® (50-100% EtOAc/hexane) to give the title product as an off white solid, 1.0 g (yield 54%). 1H NMR (300 MHz, DMSO-d6) δ 8.60 (s, 1 H), 8.05 (d, 2 H), 8.0 (s, 1 H), 7.90 (d, 1 H), 7.70 (s, 1 H), 7.60-7.40 (m, 7 H), 7.25 (d, 1 H), 7.20 (s, 1 H), 5.70 (s, 2 H), 4.0 (m, 2 H), 3.0 (m, 2 H), 1.70 (m, 2 H), 1.2-1.0 (m, 5 H); ES-MS m/z 5467.27 [M+H]+, HPLC RT (min) 2.79.

Aufarbeitung

  1. customThe reaction was irradiated in a microwave reactor at 150° C. for 10 min
  2. temperatureAfter cooling the mixture
  3. customwas partitioned between EtOAc and H2O
  4. customThe organic phase was separated
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe crude was purified by Biotage® (50-100% EtOAc/hexane)

Quellen und Nachweise

ORD-Eintrag
ord-bd3aac42f33446979aeb8df1d6f1e355
Quelldatensatz
uspto-grants-2013_04
Patentnummer
US08431695B2

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