[Br:1][C:2]1[C:10]2[C:5]([NH:6][CH:7]=[N:8][C:9]=2[Cl:11])=[N:4][CH:3]=1.[O:12]1[CH2:15][CH:14](O)[CH2:13]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>O1CCOCC1>[Br:1][C:2]1[C:10]2[C:9]([Cl:11])=[N:8][CH:7]=[N:6][C:5]=2[N:4]([CH:14]2[CH2:15][O:12][CH2:13]2)[CH:3]=1
To 5-bromo-4-chloro-1H-pyrrolo[2,3-d]pyrimidine (300 mg, 1.291 mmol) were added 3-oxetanol (287 mg, 3.87 mmol), polymer bound triphenylphosphine (860 mg, 2.58 mmol) resin and 1,4-Dioxane (2 mL) into a 5 mL microwave vial then DEAD (0.409 mL, 2.58 mmol) was added. The reaction vial was then capped and heated in microwave reactor for 15 minutes at 85° C. The reaction was not complete so it was heated for a total of 1 hr and the reaction was filtered, concentrated, diluted with EtOAc (10 mL) then washed water (10 ml). The water was back extracted with EtOAc (2×10 ml). The organics were combined then washed with brine, dried over MgSO4, filtered and concentrated. The crude was loaded on to a 10 g Biotage column and purified with 0 to 40% EtOAc in Hexane gradient over 30 minutes to afford 5-bromo-4-chloro-7-(3-oxetanyl)-7H-pyrrolo[2,3-d]pyrimidine (157 mg 42.2% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 8.70 (s, 1H), 8.45 (s, 1H), 5.95 (t, J=7.07 Hz, 1H), 4.96-5.04 (m, J=7.07, 7.33, 7.45, 7.45 Hz, 4H).
Wird geladen…
