Ethylenediamine → 2-(6-chloro-1-methylindazol-3-yl)-N-[(2R)-1-(3-cyanoazetidin-1-yl)-1-oxopropan-2-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 245797Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 245797
[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:41])[C@H:8]([NH:10][C:11]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[C:19]([C:22]4[C:30]5[C:25](=[CH:26][C:27]([Cl:31])=[CH:28][CH:29]=5)[N:24]([CH3:32])[N:23]=4)[N:20]=3)[N:15](COCC[Si](C)(C)C)[CH:14]=2)=[O:12])[CH3:9])[CH2:4]1)#[N:2].FC(F)(F)C(O)=O.C(N)CN>ClCCl>[C:1]([CH:3]1[CH2:4][N:5]([C:7](=[O:41])[C@H:8]([NH:10][C:11]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[C:19]([C:22]4[C:30]5[C:25](=[CH:26][C:27]([Cl:31])=[CH:28][CH:29]=5)[N:24]([CH3:32])[N:23]=4)[N:20]=3)[NH:15][CH:14]=2)=[O:12])[CH3:9])[CH2:6]1)#[N:2]

Komponenten

5

Edukt 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712861952-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide

Produkt 1

HCID 712886022-(6-chloro-1-methylindazol-3-yl)-N-[(2R)-1-(3-cyanoazetidin-1-yl)-1-oxopropan-2-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideAusbeute 34,8 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

In a round-bottomed flask, 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide (154 mg, 0.23 mmol) was dissolved in dichloromethane (1.2 ml) and trifluoroacetic acid (0.72 ml, 9.35 mmol) was added. The orange reaction mixture was stirred at room temperature for 2 h then concentrated. The residue was redissolved in dichloromethane (1.2 ml) and ethylenediamine (1.0 ml, 14.8 mmol) was added. The solution was stirred at room temperature for 1.5 h then quenched with water and diluted with ethyl acetate. The resultant suspension was filtered, washing with water (hot), ethyl acetate and dichloromethane then dried under high vacuum to afford 37 mg (33%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide as a white powder. MS: (M+H)+=463; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 12.70 (br. s., 1H), 9.15 (s, 1H), 8.73 (d, J=8.7 Hz, 1H), 8.47 (t, J=7.4 Hz, 2H), 7.98 (s, 1H), 7.27 (d, J=8.7 Hz, 1H), 4.47-4.84 (m, 3H), 4.18 (s, 3H), 4.02-4.32 (m, 2H), 3.86 (br. s., 1H), 1.42 (d, J=4.5 Hz, 3H).

Aufarbeitung

  1. concentrationthen concentrated
  2. dissolutionThe residue was redissolved in dichloromethane (1.2 ml)
  3. stirringThe solution was stirred at room temperature for 1.5 h
  4. customthen quenched with water
  5. additiondiluted with ethyl acetate
  6. filtrationThe resultant suspension was filtered
  7. washwashing with water (hot), ethyl acetate and dichloromethane
  8. customthen dried under high vacuum

Quellen und Nachweise

ORD-Eintrag
ord-ac05026954c74c6d812efa0d4496cf4e
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658646B2

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