Hydrochloric Acid → HCID 86677949, Verbindung

HRID 246104

Reaktionsgleichung

Reaktionsgleichung von HRID 246104
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:17]=[C:16]4[C:18]([C:29](O)=[O:30])=[CH:19][N:20]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:15]4=[N:14][CH:13]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1.C([N:35]([CH2:39][CH3:40])[CH:36](C)C)(C)C.CN(C)CCCN=C=NCC.CC1CN1.Cl>ClCCl.CN(C)C1C=CN=CC=1.C(OCC)(=O)C.O>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:17]=[C:16]4[C:18]([C:29]([N:35]5[CH2:36][CH:39]5[CH3:40])=[O:30])=[CH:19][N:20]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:26])([CH3:28])[CH3:27])[C:15]4=[N:14][CH:13]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1

Komponenten

10

Edukt 5

HCID 313Hydrochloric AcidHCID 63772-MethylaziridineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 712796712-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

Produkt 1

HCID 86677949HCID 86677949, VerbindungAusbeute 64,6 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

2-(6-Chloro-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxylic acid (100 mg, 0.218 mmol) was suspended in dichloromethane (2.2 ml). 4-Dimethylaminopyridine (5.3 mg, 0.044 mmol), N,N-diisopropylethylamine (76 ul, 0.44 mmol) and then 1-(3-(dimethylamino)-propyl)-3-ethylcarbodiimide (84 mg, 0.44 mmol) were added. The solution was stirred for 5 min then cooled in an ice bath. 2-Methylaziridine (23 ul, 0.33 mmol) was added and the reaction was warmed to room temperature. Stirring was continued until judged to be complete by TLC then water, dilute HCl and ethyl acetate were added. The aqueous layer was extracted once more with ethyl acetate and the combined organic layers were washed with sodium bicarbonate solution and dried over sodium sulfate. After evaporation the residue was purified by silica gel chromatography (ethyl acetate/hexanes) to give 70 mg (64%) of [2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-(2-methyl-aziridin-1-yl)-methanone. 1H NMR (300 MHz, CDCl3) δ ppm 9.23 (s, 1H) 8.76 (d, J=8.7 Hz, 1H) 8.33 (s, 1H) 7.44 (s, 1H) 7.24 (d, J=8.7 Hz, 1H) 5.73 (s, 2H) 4.14 (s, 3H) 3.56-3.65 (m, 6H) 2.80-2.91 (m, 1H) 2.59 (d, J=6.0 Hz, 1H) 2.33 (d, J=3.8 Hz, 1H) 1.41 (d, J=5.3 Hz, 3H) 0.89-0.99 (m, 2H)-0.05 (s, 9H).

Aufarbeitung

  1. temperaturethen cooled in an ice bath
  2. stirringStirring
  3. extractionThe aqueous layer was extracted once more with ethyl acetate
  4. washthe combined organic layers were washed with sodium bicarbonate solution
  5. dry with materialdried over sodium sulfate
  6. customAfter evaporation the residue
  7. customwas purified by silica gel chromatography (ethyl acetate/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-fca5b22889e7498f9094416f8bddae61
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658646B2

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