反应 #590734

反应方程式

1,4-dioxane

N-(4-(7-Bromoquinolin-4-yloxy)phenyl)-4-phenylphthalazin-1-amine

morpholine

tert-butanol

DavePhos

sodium tert-butoxide

DavePhos

NaOt-Bu

→

title compound

N-(4-(7-Morpholinoquinolin-4-yloxy)phenyl)-4-phenylphthalazin-1-amine

溶剂

CH2Cl2

反应条件

后处理

1. 1
   其他equipped with a stir bar
2. 2
   其他The tube was purged with argon
3. 3
   其他The tube was sealed
4. 4
   温度The reaction was cooled to rt
5. 5
   其他placed in a preheated oil bath at 100° C
6. 6
   其他at 1.434 min
7. 7
   浓缩The filtrate was concentrated
8. 8
   其他The product was purified by column chromatography on silica gel eluting with 70:30
9. 9
   其他to obtain top spot
10. 10
    洗涤washing with 60:40 CH2Cl2
11. 11
    其他(90:10:1 CH2Cl2:MeOH:NOH) to collect the product
12. 12
    workup.ADDITIONFractions containing the product
13. 13
    浓缩were concentrated
14. 14
    其他A yellow solid was obtained
15. 15
    其他dried in the vacuum oven
16. 16
    其他The yellow solid was further purified by RPLC on the acidic Gilson workstation
17. 17
    workup.ADDITIONFractions containing the product
18. 18
    workup.ADDITIONwere diluted with CH2Cl2 and neutralized with sat. NaHCO3
19. 19
    其他The organic layer was separated
20. 20
    干燥dried over MgSO4
21. 21
    过滤filtered
22. 22
    浓缩concentrated
23. 23
    其他Yellow solid was obtained

实验过程

The title compound was prepared according to a method described in Ali, M. H.; Buchwald, S. L. J. Org. Chem. 2001, 66, 2560. Pd2(dba)3(21 mg, 23 μmol), DavePhos (18 mg, 46 μmol), and sodium tert-butoxide (110 mg, 1141 μmol) were added into a screw-capped tube equipped with a stir bar. The tube was purged with argon. N-(4-(7-Bromoquinolin-4-yloxy)phenyl)-4-phenylphthalazin-1-amine (237 mg, 456 μmol) was added to the purged tube, followed by morpholine (159 μl, 1825 μmol), 1,4-dioxane (2074 μl, 456 μmol), and tert-butanol (1037 μl, 456 μmol). The tube was sealed and heated to 100° C. in an oil bath for 1 h. The reaction was cooled to rt, and 22 mg of Pd2(dba)3, 20 mg of DavePhos, and 80 mg of NaOt-Bu were added. The tube was resealed and placed in a preheated oil bath at 100° C. After another 3.5 h, LCMS showed mainly product at 1.434 min as [M+H]+=526. The mixture was passed through a pad of celite with an aid of CH2Cl2. The filtrate was concentrated. The product was purified by column chromatography on silica gel eluting with 70:30 to obtain top spot, then washing with 60:40 CH2Cl2:(90:10:1 CH2Cl2:MeOH:NOH) to collect the product. Fractions containing the product were concentrated. A yellow solid was obtained and dried in the vacuum oven. The yellow solid was further purified by RPLC on the acidic Gilson workstation. Fractions containing the product were diluted with CH2Cl2 and neutralized with sat. NaHCO3. The organic layer was separated, dried over MgSO4, filtered, and concentrated. Yellow solid was obtained. HPLC showed 100% pure. LCMS confirmed product. MS Calcd for C33H27N5O2: [M]+=525. Found: [M+H]+=526.

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