2-(Pyrrolidin-3-yl)propan-2-ol → 2-(1-(3-(4-(Pyridin-2-ylamino)phenoxy)pyrazin-2-YL)pyrrolidin-3-YL)propan-2-OL
Reaction equation
Cl[C:2]1[C:3]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=3)=[CH:11][CH:10]=2)=[N:4][CH:5]=[CH:6][N:7]=1.[NH:22]1[CH2:26][CH2:25][CH:24]([C:27]([OH:30])([CH3:29])[CH3:28])[CH2:23]1>CS(C)=O>[N:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[NH:15][C:12]1[CH:13]=[CH:14][C:9]([O:8][C:3]2[C:2]([N:22]3[CH2:26][CH2:25][CH:24]([C:27]([OH:30])([CH3:29])[CH3:28])[CH2:23]3)=[N:7][CH:6]=[CH:5][N:4]=2)=[CH:10][CH:11]=1Participants
Conditions
- Temperature
- 80 °C
Procedure
A mixture of N-(4-(3-chloropyrazin-2-yloxy)phenyl)pyridin-2-amine (0.150 g, 0.502 mmol) and 2-(pyrrolidin-3-yl)propan-2-ol (0.187 g, 1.447 mmol) in 3 mL of DMSO was sealed in a microwave tube and heated at 80° C. overnight. The reaction was cooled to RT, filtered and purified by purified by reverse-phase HPLC (Gilson; Gemini-NX 10m C18 110A AXIA, 100×50 mm column) eluting with 0.1% TFA-H2O:0.1% TFA CH3CN (9:1→1:9). The fractions containing the desired product were combined and basified with satd NaHCO3 and extracted with DCM (3×). The combined organic layers were dried over Na2SO4 filtered and concentrated to dryness to give the title compound as a light-yellow crystalline solid. MS (ESI, pos. ion) m/z: 392 (M+1). IC50 (uM) 0.02882.
Workup
- customwas sealed in a microwave tube
- temperatureThe reaction was cooled to RT
- filtrationfiltered
- custompurified
- customby purified by reverse-phase HPLC (Gilson
- washGemini-NX 10m C18 110A AXIA, 100×50 mm column) eluting with 0.1% TFA-H2O
- additionThe fractions containing the desired product
- extractionextracted with DCM (3×)
- dry with materialThe combined organic layers were dried over Na2SO4
- filtrationfiltered
- concentrationconcentrated to dryness
Sources & evidence
- ORD record
- ord-84fd81c7ee46444bbfac5ba6c779f3c4
- Source dataset
- uspto-grants-2014_01
- Patent number
- US08637500B2
Reaction notes
Loading…