Triethylamine → (7R,8aS)-N-(2-chloro-5-cyanopyrimidin-4-yl)-octahydro-5,5-dimethylindolizin-7-amine
Reaction equation
[NH2:1][C:2]([C:4]1[C:5]([NH:11][C@@H:12]2[CH2:20][C@H:19]3[N:15]([CH2:16][CH2:17][CH2:18]3)[C:14]([CH3:22])([CH3:21])[CH2:13]2)=[N:6][C:7]([Cl:10])=[N:8][CH:9]=1)=O.C(N(CC)CC)C.FC(F)(F)C(OC(=O)C(F)(F)F)=O>C1COCC1>[Cl:10][C:7]1[N:6]=[C:5]([NH:11][C@@H:12]2[CH2:20][C@H:19]3[N:15]([CH2:16][CH2:17][CH2:18]3)[C:14]([CH3:21])([CH3:22])[CH2:13]2)[C:4]([C:2]#[N:1])=[CH:9][N:8]=1Participants
5
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
To a mixture of (7R,8aS)—N-(5-aminocarbonyl-2-chloropyrimidin-4-yl)-octahydro-5,5-dimethylindolizin-7-amine (1.3 g) and triethylamine (1.72 mL) in THF (50 mL) was added trifluoroacetic anhydride (1.33 mL) at −78° C. After stifling for 2 h, the reaction was quenched with ice (150 mL). The aqueous solution was extracted with EtOAc (6×150 mL). The organic layers were evaporated under vacuum and the residue was purified by CombiFlash chromatography on silica gel (2N NH3 in MeOH/CH2Cl2=0-20%) to give the desired product (1.1 g, 89%).
Workup
- customthe reaction was quenched with ice (150 mL)
- extractionThe aqueous solution was extracted with EtOAc (6×150 mL)
- customThe organic layers were evaporated under vacuum
- customthe residue was purified by CombiFlash chromatography on silica gel (2N NH3 in MeOH/CH2Cl2=0-20%)
Sources & evidence
- ORD record
- ord-154f78aac52948a684a29831b0bc5d8c
- Source dataset
- uspto-grants-2015_10
- Patent number
- US09169249B2
Reaction notes
Loading…