반응 #720539

반응 방정식

N-(2-chloro-5-fluoropyrimidin-4-yl)octahydroindolizin-7-amine

1-(5-amino-2-cyclopropyl-4-fluorophenyl)-4-methyl-1H-tetrazol-5-one

para-toluenesulfonic acid monohydrate

→

product

수율 47.0%

(±)-1-(5-(5-fluoro-4-(octahydroindolizin-7-ylamino)pyrimidin-2-ylamino)-2-cyclopropyl-4-fluorophenyl)-4-methyl-1H-tetrazol-5(4H)one

수율 47.0%

용매

isopropyl alcohol

반응 조건

후처리

1. 1
   기타prepared
2. 2
   온도After cooling
3. 3
   농축the mixture was concentrated under vacuum
4. 4
   기타to leave a crude residue
5. 5
   기타The residue was purified by preparative high-performance liquid chromatography
6. 6
   기타to give a solid
7. 7
   기타The solid was partitioned between EtOAc (20 ml) and 1N NaOH (20 ml)
8. 8
   추출The aqueous layer was extracted with EtOAc (2×20 ml)
9. 9
   건조the combined organic extracts were dried (MgSO4)
10. 10
    여과filtered
11. 11
    기타the solvent removed in vacuo

실험 절차

A mixture of N-(2-chloro-5-fluoropyrimidin-4-yl)octahydroindolizin-7-amine (54 mg, 0.2 mmol), 1-(5-amino-2-cyclopropyl-4-fluorophenyl)-4-methyl-1H-tetrazol-5-one (52 mg, 0.21 mmol; prepared according to US20110130415 pages 43-48, which is hereby incorporated by reference in its entirety) and para-toluenesulfonic acid monohydrate (38 mg, 0.2 mmol) in isopropyl alcohol (3 ml) were combined in a sealed vial, heated to 70° C. and stirred for 2 days. After cooling, the mixture was concentrated under vacuum to leave a crude residue. The residue was purified by preparative high-performance liquid chromatography to give a solid. The solid was partitioned between EtOAc (20 ml) and 1N NaOH (20 ml). The aqueous layer was extracted with EtOAc (2×20 ml) and the combined organic extracts were dried (MgSO4), filtered and the solvent removed in vacuo to leave the product (46 mg, 47%) as a solid after freeze-drying from MeCN/H2O.

출처