Ethylenediamine → 2-(3-chloro-6-fluoro-imidazo[1,5-a]pyridin-1-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide

HRID 245868Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 245868
[CH3:1][O:2][CH2:3][C@@H:4]([NH:6][C:7]([C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([C:18]3[N:19]=[C:20]([Cl:28])[N:21]4[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:22]=34)[N:16]=2)[N:11](COCC[Si](C)(C)C)[CH:10]=1)=[O:8])[CH3:5].FC(F)(F)C(O)=O.C(N)CN>ClCCl>[CH3:1][O:2][CH2:3][C@@H:4]([NH:6][C:7]([C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([C:18]3[N:19]=[C:20]([Cl:28])[N:21]4[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:22]=34)[N:16]=2)[NH:11][CH:10]=1)=[O:8])[CH3:5]

Komponenten

5

Edukt 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712881612-(3-chloro-6-fluoro-imidazo[1,5-a]pyridin-1-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide

Produkt 1

HCID 712881802-(3-chloro-6-fluoro-imidazo[1,5-a]pyridin-1-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amideAusbeute 77 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

In a round-bottomed flask, 2-(3-chloro-6-fluoro-imidazo[1,5-a]pyridin-1-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide (36 mg, 0.068 mmol) was dissolved in dichloromethane (0.4 ml) and trifluoroacetic acid (0.22 ml, 2.86 mmol) was added. The reaction was stirred at room temperature for 2 h then concentrated. The residue was dissolved in dichloromethane (0.4 ml) and ethylenediamine (0.3 ml, 4.3 mmol) was added. The reaction mixture was stirred at room temperature for 1 h then quenched with water and diluted with ethyl acetate. The resulting suspension was filtered, washed with hot water and ethyl acetate and dried under high vacuum to provide 21 mg (77%) of 2-(3-chloro-6-fluoro-imidazo[1,5-a]pyridin-1-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide as a yellow powder. MS: (M+H)+=403; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 12.01 (br. s, 1H), 9.03 (s, 1H), 8.58 (d, J=3.8 Hz, 1H), 8.49 (dd, J=10.0, 5.5 Hz, 1H), 8.40 (s, 1H), 8.10 (d, J=8.3 Hz, 1H), 7.18-7.29 (m, 1H), 4.39 (d, J=7.9 Hz, 1H), 3.50 (qd, J=9.9, 4.3 Hz, 2H), 3.30 (s, 3H), 1.31 (d, J=6.8 Hz, 3H).

Aufarbeitung

  1. concentrationthen concentrated
  2. dissolutionThe residue was dissolved in dichloromethane (0.4 ml)
  3. stirringThe reaction mixture was stirred at room temperature for 1 h
  4. customthen quenched with water
  5. additiondiluted with ethyl acetate
  6. filtrationThe resulting suspension was filtered
  7. washwashed with hot water and ethyl acetate
  8. customdried under high vacuum

Quellen und Nachweise

ORD-Eintrag
ord-ab58afe598ee46d698837d81a69757c7
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658646B2

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