Ethylenediamine → 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((1R,2R)-2-hydroxy-1-hydroxymethyl-propyl)-amide

HRID 246176Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 246176
[OH:1][C@H:2]([CH3:37])[C@H:3]([NH:6][C:7]([C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([C:18]3[C:26]4[C:21](=[CH:22][C:23]([F:27])=[CH:24][CH:25]=4)[N:20]([CH3:28])[N:19]=3)[N:16]=2)[N:11](COCC[Si](C)(C)C)[CH:10]=1)=[O:8])[CH2:4][OH:5].C(O)(C(F)(F)F)=O.C(N)CN>ClCCl>[OH:1][C@H:2]([CH3:37])[C@H:3]([NH:6][C:7]([C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([C:18]3[C:26]4[C:21](=[CH:22][C:23]([F:27])=[CH:24][CH:25]=4)[N:20]([CH3:28])[N:19]=3)[N:16]=2)[NH:11][CH:10]=1)=[O:8])[CH2:4][OH:5]

Komponenten

5

Edukt 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712883452-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((1R,2R)-2-hydroxy-1-hydroxymethyl-propyl)-amide

Produkt 1

HCID 712884002-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((1R,2R)-2-hydroxy-1-hydroxymethyl-propyl)-amideAusbeute 40 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

In a 10 mL round-bottom flask, 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((1R,2R)-2-hydroxy-1-hydroxymethyl-propyl)-amide (30 mg, 0.057 mmol) and TFA (0.3 ml, 3.9 mmol) were combined with dichloromethane (1 ml) to give an orange solution. The reaction mixture was stirred at room temperature for 2.5 h then concentrated under reduced pressure. The resultant crude solid was dissolved in dichloromethane (1 mL) and ethylenediamine (0.10 ml, 1.5 mmol) was added. The reaction mixture was stirred at room temperature for 18 h then concentrated and the residue was precipitated with water. The suspension was stirred for 1 h and the crude solid collected by filtration. The crude solid was purified by trituration (hot dichloromethane/heptane) to afford 9 mg (40%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((1R,2R)-2-hydroxy-1-hydroxymethyl-propyl)-amide as a light yellow solid. MS: [M+H]+=399; 1H NMR (DMSO-d6) δ: 12.61 (br. s., 1H), 9.16 (s, 1H), 8.83 (dd, J=8.9, 5.5 Hz, 1H), 8.44 (s, 1H), 8.15 (d, J=9.4 Hz, 1H), 7.64 (dd, J=9.8, 1.9 Hz, 1H), 7.15 (td, J=9.3, 1.9 Hz, 1H), 5.07 (d, J=4.2 Hz, 1H), 4.85 (t, J=4.9 Hz, 1H), 4.15 (s, 3H), 3.98-4.24 (m, 2H), 3.54-3.71 (m, 2H), 1.13 (d, J=6.0 Hz, 3H).

Aufarbeitung

  1. customto give an orange solution
  2. concentrationthen concentrated under reduced pressure
  3. dissolutionThe resultant crude solid was dissolved in dichloromethane (1 mL)
  4. stirringThe reaction mixture was stirred at room temperature for 18 h
  5. concentrationthen concentrated
  6. customthe residue was precipitated with water
  7. stirringThe suspension was stirred for 1 h
  8. filtrationthe crude solid collected by filtration
  9. customThe crude solid was purified by trituration (hot dichloromethane/heptane)

Quellen und Nachweise

ORD-Eintrag
ord-c4c9db4f5c52473181221e08b70e74ae
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658646B2

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