Diisopropylethylamine → tert-butyl (3-(2-((4-methoxy-6-(4-methylpiperazin-1-yl)pyridin-3-yl)amino)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)carbamate

HRID 527419Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 527419
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([N:9]2[CH2:14][CH2:13][N:12]([CH3:15])[CH2:11][CH2:10]2)[N:6]=[CH:5][C:4]=1[NH2:16].CS([C:20]1[N:21]=[CH:22][C:23]2[CH:29]=[CH:28][C:27](=[O:30])[N:26]([C:31]3[CH:32]=[C:33]([NH:37][C:38](=[O:44])[O:39][C:40]([CH3:43])([CH3:42])[CH3:41])[CH:34]=[CH:35][CH:36]=3)[C:24]=2[N:25]=1)=O.CCN(C(C)C)C(C)C>C(O)(C)(C)C>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([N:9]2[CH2:14][CH2:13][N:12]([CH3:15])[CH2:11][CH2:10]2)[N:6]=[CH:5][C:4]=1[NH:16][C:20]1[N:21]=[CH:22][C:23]2[CH:29]=[CH:28][C:27](=[O:30])[N:26]([C:31]3[CH:32]=[C:33]([NH:37][C:38](=[O:44])[O:39][C:40]([CH3:42])([CH3:41])[CH3:43])[CH:34]=[CH:35][CH:36]=3)[C:24]=2[N:25]=1

Komponenten

5

Edukt 3

HCID 81531DiisopropylethylamineHCID 86732007tert-butyl (3-(2-(methylsulfinyl)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)carbamateHCID 867320304-Methoxy-6-(4-methylpiperazin-1-yl)pyridin-3-amine

Produkt 1

HCID 86732031tert-butyl (3-(2-((4-methoxy-6-(4-methylpiperazin-1-yl)pyridin-3-yl)amino)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)carbamateAusbeute 77 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6386tert-ButanolLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

4-Methoxy-6-(4-methylpiperazin-1-yl)pyridin-3-amine (8a; 1.22 g, 5.49 mmol), tert-butyl (3-(2-(methylsulfinyl)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)carbamate (52; 1.40 g, 3.50 mmol) were treated with tert-butanol (20 mL) and DIEA (1.53 mL, 8.74 mmol) and heated to 85° C. overnight (20 h) in a 250 mL round-bottomed flask with a reflux condenser. The reaction mixture was concentrated on the rotovap and the crude solid was suspended in Et2O and filtered affording the crude tert-butyl (3-(24(4-methoxy-6-(4-methylpiperazin-1-yl)pyridin-3-yl)amino)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)carbamate (8b; 1.50 g, 2.69 mmol, 77% yield) as a brownish-yellow amorphous solid. m/z (ESI, +ve ion) 559.0 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.48 (1H, br. s.), 8.65 (1H, br. s.), 8.54 (1H, s), 7.86 (1H, d, J=9.4 Hz), 7.82 (1H, s), 7.43 (1H, d, J=8.0 Hz), 7.37 (2H, br. s.), 6.81 (1H, br. s.), 6.38 (1H, d, J=9.4 Hz), 6.29 (1H, br. s.), 3.73 (3H, s), 3.45 (4H, br. s.), 2.40 (4H, br. s.), 2.24 (3H, s), 1.47 (9H, s).

Aufarbeitung

  1. concentrationThe reaction mixture was concentrated on the rotovap
  2. filtrationfiltered

Quellen und Nachweise

ORD-Eintrag
ord-43ae3f34b10b4c55bf82afe94ff0ba7a
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09346801B2

Notizen zur Reaktion

Wird geladen…