Reaktion #1250342

Reaktionsgleichung

2-phenyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinazoline

7-cyclobutyl-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine

Na2CO3

→

title compound

7-Cyclobutyl-5-(2-phenylquinazolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeA flask equipped with a reflux condenser
2. 2
   SonstigeThe reaction setup was evacuated
3. 3
   workup.ADDITIONrefilled with Ar (3×)
4. 4
   Sonstigethe system was evacuated
5. 5
   workup.ADDITIONrefilled with Ar (3×) again
6. 6
   workup.ADDITIONDegassed solvent mixture H2O-DMF (1:5 v/v, 5 mL) was added
7. 7
   SonstigeThe resulting orange-light brown solution was partitioned between DCM (˜80 mL) and H2O (10 mL)
8. 8
   ExtraktionThe aqueous layer was extracted with DCM (3×)
9. 9
   WaschenCombined organics were washed with brine
10. 10
    Trocknendried (Na2SO4)
11. 11
    Einengenconcentrated under reduced pressure (125 mg)
12. 12
    SonstigePurification by flash chromatography (silica gel, 25 g, 0-2% MeOH in DCM)

Vorschrift

A flask equipped with a reflux condenser was charged with 2-phenyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinazoline (67 mg, 0.20 mmol), 7-cyclobutyl-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine (64 mg, 0.20 mmol) and Na2CO3 (56 mg, 0.51 mmol). The reaction setup was evacuated and refilled with Ar (3×). Pd(PPh3)4 (24 mg, 0.021 mmol) was added swiftly minimizing exposure to air and the system was evacuated and refilled with Ar (3×) again. Degassed solvent mixture H2O-DMF (1:5 v/v, 5 mL) was added and the reaction mixture was heated at 80° C. for 42 h. The resulting orange-light brown solution was partitioned between DCM (˜80 mL) and H2O (10 mL). The aqueous layer was extracted with DCM (3×). Combined organics were washed with brine, dried (Na2SO4) and concentrated under reduced pressure (125 mg). Purification by flash chromatography (silica gel, 25 g, 0-2% MeOH in DCM) provided the title compound as a pale yellow solid; The material was also later triturated (hexane 2×, Et2O 1×); 1H NMR (400 MHz, CDCl3) δ 9.46 (d, J=0.8 Hz, 1H), 8.65-8.58 (m, 2H), 8.35 (s, 1H), 8.16 (s, 1H), 8.00 (d, J=8.4 Hz, 1H), 7.75 (dd, J=2.0 Hz, 8.4 Hz, 1H), 7.56-7.46 (m, 3H), 7.39 (s, 1H), 5.44 (br, 2H), 5.33 (quintet, J=8.2 Hz, 1H), 2.67-2.40 (m, 4H), 2.17-1.89 (m, 2H). MS (ES+): m/z 393.1 (100) [MH+]; HPLC: tR=2.91 min (OpenLynx, polar—5 min).

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