With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.19788-37-5,4-(Chloromethyl)-3,5-dimethylisoxazole,as a common compound, the synthetic route is as follows.
The allyl alcohol (20 mg, 0.035 mmol, Example 952) was dissolved in THF (1.00 rnL) and cooled to 0 C. Sodium hydride (60% dispersion; 840 rng, 0.350 rnmoi) was added and the mixture was stirred for 30 minutes. 4-(chloromethvi)-3.5-dimethviisoxazole (0022 mL. 0.175 rnrnoi) was then addedand the resulting mixture was stirred for 4,5 hours, Three more aliquol of reagents were added and the slurry was stirred at room temperature for 4.5 days. Thereaction was quenched with water and acidified with IN HC1 to pH5. The mixture was extracted with ethyl acetate (2 x 30 mL). The combined organiclayers were washed with brine (1 x 20 mL) and dried over magnesium sulfate.The crude material was purified by reverse-phase preparative HPLC using aPhenomenex Luna column. 10 micron. C8(2), 100 A. 150x 30mm. 0.1% TFA inCH3CN/H20, gradient 50% to 80% over 25 mm to provide (IS,3R,6],7R,8E)- 15Wspiro [naphthaIene 1,22-[2Oioxa[ 131 thia[ 1, i4ldiazatetracycio[1 47.203?6.0?924ipentacosa[8, 16,1 8,24itetrae nj-IS-one 13,13-dioxide (10mg, 0.015 mmol, 42 /yleId). ?HNMR (400MHz. CDCIs) oe 816 (s, 1 H), 7.71 (d, J=8.4 Hz, 1 H), 7.30 (s, I H), 7.18 (dd. 3=8.4, 2.3 Flz. I H), 7.09 (d. J::::2.3 Hz. I H), 695 (s, 2 Fl), 572 (dt, j:::16,O Hz, 4.7 Hz, I H),5-46 (dd, J=158, 8.4 Hz, I H), 4.65 (d, J=12. 1 Hz, 1 H), 4,13-426 (m, 1 H). 4.11 (s, 2 H), 4.03 (d, J:::12 1 Hz, I H). 396 (d, j:::14.7 Hz, 1 H), 3.59-3.71 (m, 2 H),3.19-3.30 (m, I H), 3.16 (d, J=14.3 Hz, 1 H), 2.86-2.98 (rn, 1 H), 2.66-2.84 (rn,H), 2.42-2.58 (in, 2 H), 2.40 (s, 3 H), 2.32 (s, 3 H), 2.08-2.22 (in, 3 H), 1.85-2.07(iii. 4 H), 1.75-185 (iii. 1 H), 1.65-1.74 (iii. 1 H), 1.50-1.64 (in. 1 H), 1.38-147(m. 2 H). rn/z (ESI, +ve ion) 680.3 (M+H)t, 19788-37-5
The synthetic route of 19788-37-5 has been constantly updated, and we look forward to future research findings.
Reference£º
Patent; AMGEN INC.; BROWN, Sean P.; BEDKE, David Karl; DEGRAFFENREID, Michael R.; FU, Jiasheng; LI, Zhihong; GONZALEZ LOPEZ DE TURISO, Felix; GONZALEZ BUENROSTRO, Ana; GRIBBLE, Jr., Michael W.; JOHNSON, Michael G.; KOHN, Todd J.; LI, Kexue; LI, Yunxiao; LIZARZABURU, Mike Elias; REW, Yosup; TAYGERLY, Joshua; WANG, Yingcai; YAN, Xuelei; YU, Ming; ZHU, Jiang; ZANCANELLA, Manuel; JIAO, Xian Yun; ZHU, Liusheng; WANG, Xianghong; MEDINA, Julio C.; DUQUETTE, Jason A.; HOUZE, Jonathan B.; VIMOLRATANA, Marc; CARDOZO, Mario G.; CHENG, Alan C.; (2426 pag.)WO2017/147410; (2017); A1;,
Isoxazole – Wikipedia
Isoxazole | C3H3NO – PubChem