Hydrochloric Acid → N-(5-((4-methoxybenzyloxy)methyl)-3-(2-methyl-9H-purin-6-yl)pyridin-2-yl)-1H-indol-4-amine

HRID 1621442Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1621442
F[C:2]1[C:7]([C:8]2[N:16]=[C:15]([CH3:17])[N:14]=[C:13]3[C:9]=2[N:10]=[CH:11][N:12]3C2CCCCO2)=[CH:6][C:5]([CH2:24][O:25][CH2:26][C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=2)=[CH:4][N:3]=1.[NH2:35][C:36]1[CH:44]=[CH:43][CH:42]=[C:41]2[C:37]=1[CH:38]=[CH:39][NH:40]2.Cl>CCO.CO.N>[CH3:34][O:33][C:30]1[CH:29]=[CH:28][C:27]([CH2:26][O:25][CH2:24][C:5]2[CH:6]=[C:7]([C:8]3[N:16]=[C:15]([CH3:17])[N:14]=[C:13]4[C:9]=3[N:10]=[CH:11][NH:12]4)[C:2]([NH:35][C:36]3[C:37]4[CH:38]=[CH:39][NH:40][C:41]=4[CH:42]=[CH:43][CH:44]=3)=[N:3][CH:4]=2)=[CH:32][CH:31]=1

Komponenten

7

Edukt 3

HCID 313Hydrochloric AcidHCID 5834314-AminoindoleHCID 595483946-(2-fluoro-5-((4-methoxybenzyloxy)methyl)pyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine

Produkt 1

HCID 178491393N-(5-((4-methoxybenzyloxy)methyl)-3-(2-methyl-9H-purin-6-yl)pyridin-2-yl)-1H-indol-4-amineAusbeute 7,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 222AmmoniaLösungsmittelHCID 702EthanolLösungsmittelHCID 887MethanolLösungsmittel2×

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

6-(2-Fluoro-5-((4-methoxybenzyloxy)methyl)pyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (171.2 mg, 0.3694 mmol) and 4-aminoindole (Aldrich, St. Louis, Mo., 69.2 mg, 0.524 mmol) were suspended in EtOH (2.0 mL) and hydrochloric acid (J. T. Baker, Phillipsburg, N.J., 5N, 0.090 mL, 0.45 mmol) was added. The flask was fitted with a reflux condenser and placed in a preheated oil bath (100° C.) and stirred for about 105 minutes. Then, the reaction was cooled to room temperature and diluted with MeOH and 2N ammonia in MeOH. The reaction was concentrated and treated with DMF and DCM and filtered. The filtrate was filtered again, and the solid was again washed with DCM. This filtrate was concentrated and purified by HPLC (10% to 100% MeCN/water with 0.1% TFA over 30 minutes with a total flow rate of 100 ml/min). The fractions with product were collected, concentrated, and filtered through a silica gel filter (about 1 inch, 10:1 DCM/2N ammonia in MeOH) to give N-(5-((4-methoxybenzyloxy)methyl)-3-(2-methyl-9H-purin-6-yl)pyridin-2-yl)-1H-indol-4-amine (13.1 mg, 7% yield). MS (ESI pos. ion) m/z 492 (M+H)+. 1H NMR (d6-DMSO, 400 MHz) δ 12.49 (s, 1H), 11.17 (s, 1H), 9.84 (s, 1H), 8.64 (s, 1H), 8.33 (s, 1H), 8.04 (d, J=6.85 Hz, 1H), 7.38-7.32 (m, 3H), 7.12-7.04 (m, 2H), 6.93 (d, J=8.80 Hz, 2H), 6.72 (s, 1H), 4.53 (s, 2H), 4.51 (s, 2H), 3.75 (s, 3H), 2.92 (s, 3H).

Aufarbeitung

  1. customThe flask was fitted with a reflux condenser
  2. customplaced in a preheated oil bath
  3. temperatureThen, the reaction was cooled to room temperature
  4. concentrationThe reaction was concentrated
  5. additiontreated with DMF and DCM
  6. filtrationfiltered
  7. filtrationThe filtrate was filtered again
  8. washthe solid was again washed with DCM
  9. concentrationThis filtrate was concentrated
  10. custompurified by HPLC (10% to 100% MeCN/water with 0.1% TFA over 30 minutes with a total flow rate of 100 ml/min)
  11. customThe fractions with product were collected
  12. concentrationconcentrated
  13. filtrationfiltered through a silica gel
  14. filtrationfilter (about 1 inch, 10:1 DCM/2N ammonia in MeOH)

Quellen und Nachweise

ORD-Eintrag
ord-fc169d0adecf477e87fff5de79a6c60b
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08772480B2

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