Potassium Carbonate → Formate

HRID 1399902Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1399902
Cl[C:2]1[N:3]=[CH:4][C:5]2[CH:10]=[CH:9][N:8]([CH3:11])[C:6]=2[N:7]=1.[CH2:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:15][CH2:14][N:13]1[CH2:22][CH:23]([OH:41])[CH2:24][NH:25][C:26]1[CH:31]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:29]=[CH:28][N:27]=1.[C:42]([O-])([O-:44])=[O:43].[K+].[K+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:15][CH2:14][N:13]1[CH2:22][CH:23]([OH:41])[CH2:24][NH:25][C:26]1[CH:31]=[C:30]([C:2]2[N:3]=[CH:4][C:5]3[CH:10]=[CH:9][N:8]([CH3:11])[C:6]=3[N:7]=2)[CH:29]=[CH:28][N:27]=1.[CH:42]([O-:44])=[O:43]

Komponenten

8

Edukt 3

HCID 11430Potassium CarbonateHCID 574158882-Chloro-7-methyl-7H-pyrrolo(2,3-d)pyrimidineHCID 86729291HCID 86729291, Verbindung

Produkt 2

HCID 283FormateAusbeute 111,1 %HCID 86729293HCID 86729293, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a solution of 2-chloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (100 mg, 0.6 mmol) in dioxane (4 ml) and H2O (1 mL) was added 1-(3,4-dihydroisoquinolin-2(1H)-yl)-3-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)amino)propan-2-ol (292 mg, 0.716 mmol), Pd(dppf)Cl2 (44 mg, 0.06 mmol) and K2CO3 (249 mg, 1.8 mmol) at 27° C. The mixture was stirred for 16 h at 100° C. After shown to be complete by TLC the reaction mixture was concentrated and the crude residue purified by prep-HPLC separation to give the desired title compound as a formate salt as a white solid (30.0 mg, 12%). 1H NMR (400 MHz, CHLOROFORM-d) ppm 3.21 (br. s., 2H) 3.31-3.39 (m, 2H) 3.53-3.71 (m, 4H) 3.93 (s, 3H) 4.34 (br. s., 1H) 4.44 (s, 2H) 6.67 (d, J=3.51 Hz, 1H) 7.17 (d, J=7.40 Hz, 1H) 7.24-7.31 (m, 3H) 7.52 (d, J=3.51 Hz, 1H) 7.63 (d, J=5.27 Hz, 1H) 7.72 (s, 1H) 7.93 (d, J=5.52 Hz, 1H) 8.40 (br. s., 2H) 9.01 (s, 1H). LCMS (m/z): 415.2 [M+H]

Aufarbeitung

  1. concentrationwas concentrated
  2. customthe crude residue purified by prep-HPLC separation

Quellen und Nachweise

ORD-Eintrag
ord-a277b6c8a0d94b3fa9ff58834ff81cf6
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08906900B2

Notizen zur Reaktion

Wird geladen…