반응 #720540

반응 방정식

(±)-2-chloro-4-(octahydro-5,5-dimethylindolizin-7-ylamino)pyrimidine-5-carbonitrile

4-cyclopropyl-2-fluoro-5-(1H-tetrazol-1-yl)benzeneamine

para-toluenesulfonic acid monohydrate

→

product

(±)-2-(4-cyclopropyl-2-fluoro-5-(1H-tetrazol-1-yl)phenylamino)-4-(octahydro-5,5-dimethylindolizin-7-ylamino)pyrimidine-5-carbonitrile

용매

isopropyl alcohol

반응 조건

후처리

1. 1
   기타prepared
2. 2
   온도After cooling
3. 3
   여과was filtered
4. 4
   기타The aqueous and organic layers were partitioned
5. 5
   추출the aqueous layer was extracted with EtOAc (2×25 ml)
6. 6
   건조The combined organic extracts were dried (MgSO4)
7. 7
   여과filtered
8. 8
   기타the solvent removed under vacuum
9. 9
   기타to leave a solid
10. 10
    건조The solid was freeze-dried from MeCN/H2O

실험 절차

A mixture of (±)-2-chloro-4-(octahydro-5,5-dimethylindolizin-7-ylamino)pyrimidine-5-carbonitrile (60 mg of 70% pure material from previous step), 4-cyclopropyl-2-fluoro-5-(1H-tetrazol-1-yl)benzeneamine (65 mg, 0.3 mmol; prepared according to U.S. patent application Ser. No. 13/188,222, filed Jul. 21, 2011, now U.S. patent application publication US2012/0022092) and para-toluenesulfonic acid monohydrate (37 mg, 0.2 mmol) in isopropyl alcohol (3 ml) were combined in a sealed vial, heated to 80° C. and stirred for 4 hours. After cooling, a precipitate emerged which was filtered. The filter cake was suspended in EtOAc (30 ml) and 1N NaOH (50 ml). The aqueous and organic layers were partitioned and the aqueous layer was extracted with EtOAc (2×25 ml). The combined organic extracts were dried (MgSO4), filtered and the solvent removed under vacuum to leave a solid. The solid was freeze-dried from MeCN/H2O to give the product (26 mg) as a solid.

출처