Ethylenediamine → 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (3-amino-cyclopentyl)-amide

HRID 245861

Reaktionsgleichung

Reaktionsgleichung von HRID 245861
C(OC(=O)[NH:7][CH:8]1[CH2:12][CH2:11][CH:10]([NH:13][C:14]([C:16]2[C:24]3[C:19](=[N:20][CH:21]=[C:22]([C:25]4[C:33]5[C:28](=[CH:29][C:30]([Cl:34])=[CH:31][CH:32]=5)[N:27]([CH3:35])[N:26]=4)[N:23]=3)[N:18](COCC[Si](C)(C)C)[CH:17]=2)=[O:15])[CH2:9]1)(C)(C)C.FC(F)(F)C(O)=O.C(N)CN>ClCCl>[NH2:7][CH:8]1[CH2:12][CH2:11][CH:10]([NH:13][C:14]([C:16]2[C:24]3[C:19](=[N:20][CH:21]=[C:22]([C:25]4[C:33]5[C:28](=[CH:29][C:30]([Cl:34])=[CH:31][CH:32]=5)[N:27]([CH3:35])[N:26]=4)[N:23]=3)[NH:18][CH:17]=2)=[O:15])[CH2:9]1

Komponenten

5

Edukt 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 71280283(3-{[2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl]-amino}-cyclopentyl)-carbamic acid tert-butyl ester

Produkt 1

HCID 712882872-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (3-amino-cyclopentyl)-amideAusbeute 78,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

In a round-bottomed flask, (3-{[2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl]-amino}-cyclopentyl)-carbamic acid tert-butyl ester (80 mg, 0.125 mmol) was dissolved in dichloromethane (0.7 ml) and trifluoroacetic acid (0.4 ml, 5.0 mmol) was added. The reaction mixture was stirred at room temperature for 3.5 h then concentrated. The residue was dissolved in dichloromethane (0.7 ml) and ethylenediamine (0.5 ml, 7.5 mmol) was added. The solution was stirred at room temperature for 2 h then quenched with water and diluted with ethyl acetate. The resultant suspension was filtered, washed with hot water and ethyl acetate and dried under high vacuum to provide 40 mg (74%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (3-amino-cyclopentyl)-amide as an off-white powder. MS: (M+H)+=410; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 9.07 (s, 1H), 8.55 (d, J=8.7 Hz, 1H), 8.40 (s, 1H), 8.24 (d, J=7.6 Hz, 1H), 7.99 (s, 1H), 7.40 (d, J=9.1 Hz, 1H), 5.54 (br. s, 2H), 4.34-4.45 (m, 1H), 4.17 (s, 3H), 3.36-3.44 (m, 1H), 2.25-2.37 (m, 1H), 2.03-2.16 (m, 1H), 1.71-1.88 (m, 2H), 1.51-1.62 (m, 1H), 1.32-1.43 (m, 1H). The isolated product was determined to be a single diastereomer of unknown relative stereochemistry by NMR analysis.

Aufarbeitung

  1. concentrationthen concentrated
  2. dissolutionThe residue was dissolved in dichloromethane (0.7 ml)
  3. stirringThe solution was stirred at room temperature for 2 h
  4. customthen quenched with water
  5. additiondiluted with ethyl acetate
  6. filtrationThe resultant suspension was filtered
  7. washwashed with hot water and ethyl acetate
  8. customdried under high vacuum

Quellen und Nachweise

ORD-Eintrag
ord-1b6d7b0f738045208712b4126fd68c21
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658646B2

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