Ammonia → 6-Fluoro-3-(1-morpholin-4-yl-ethyl)-[1,2,4]triazolo[4,3-a]pyridine
Reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][NH:9][C:10](=O)[CH:11]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[CH3:12])=[N:6][CH:7]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCN(CC)CC.ClC(Cl)(Cl)C(Cl)(Cl)Cl.N>C1COCC1.CO.C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:10]([CH:11]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[CH3:12])=[N:9][N:8]=2)[CH:7]=1Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 3
Procedure
To a solution of Intermediate 46a (3.43 g, 12.8 mmol), Ph3P (6.71 g, 25.6 mmol) and Et3N (7.14 mL, 51.2 mmol) in THF (75 mL) at 0° C. was added hexachloroethane (6.06 g, 25.6 mmol) and the solution stirred at RT for 4 h. The brown suspension was filtered and the solid washed with THF (10 mL). The combined organics were applied to an SCX-2 cartridge, which was washed with DCM-MeOH (1:1, 100 mL) and MeOH (100 mL). The product was eluted with 2M NH3 in MeOH; concentration in vacuo gave an off-white solid. FCC, using 1-5% [2M NH3 in MeOH] in DCM, gave the title compound as an off-white solid (1.70 g, 53%). 1H NMR (300 MHz, CDCl3): 1.66 (3H, d, J 6.8), 2.45-2.60 (4H, m), 3.63-3.76 (4H, m), 4.28 (1H, q, J 6.8), 7.21 (1H, ddd, J 10.0, 7.5, 2.3), 7.76 (1H, ddd, J 10.0, 4.9, 0.9), 8.50 (1H, ddd, J 3.9, 2.3, 0.9).
Workup
- filtrationThe brown suspension was filtered
- washthe solid washed with THF (10 mL)
- washwas washed with DCM-MeOH (1:1, 100 mL) and MeOH (100 mL)
- washThe product was eluted with 2M NH3 in MeOH
- concentrationconcentration in vacuo
- customgave an off-white solid
Sources & evidence
- ORD record
- ord-6d422f6cc8ba4d089617969aa374652a
- Source dataset
- uspto-grants-2016_04
- Patent number
- US09315503B2
Reaction notes
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