Ammonia → 6-Fluoro-3-((S)-2-methyl-piperidin-1-yl)-[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]([N:12]2[CH2:17][CH2:16][CH2:15][CH2:14][C@@H:13]2[CH3:18])=O)=[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]([N:12]3[CH2:17][CH2:16][CH2:15][CH2:14][C@@H:13]3[CH3:18])=[N:9][N:8]=2)[CH:7]=1Participants
9
Reactant 5
Product 1
Reagents, catalysts & solvents 3
Procedure
To a solution of Intermediate 81b (657 mg, 2.60 mmol), Ph3P (1.37 g, 5.21 mmol) and Et3N (1.45 mL, 10.4 mmol) in THF (20 mL) at 0° C. was added hexachloroethane (1.23 g, 5.21 mmol) and the resulting yellow suspension was stirred at RT for 2 h, and at reflux for 19 h. The cooled solution was filtered and concentrated in vacuo. The brown oil was redissolved in MeOH (3 mL) and applied to an SCX-2 cartridge (20 g), washing with MeOH (100 mL). The product was eluted with 2M NH3 in MeOH (75 mL); concentration in vacuo gave a brown oil. FCC, using 1-5% [2M NH3 in MeOH] in DCM, gave the title compound as a brown oil (542 mg, 89%). LCMS (Method 3): Rt 3.00 min, m/z 235 [MH+].
Workup
- temperatureat reflux for 19 h
- filtrationThe cooled solution was filtered
- concentrationconcentrated in vacuo
- dissolutionThe brown oil was redissolved in MeOH (3 mL)
- washwashing with MeOH (100 mL)
- washThe product was eluted with 2M NH3 in MeOH (75 mL)
- concentrationconcentration in vacuo
- customgave a brown oil
Sources & evidence
- ORD record
- ord-6b8f464355224d129d944b99ec956ddd
- Source dataset
- uspto-grants-2015_09
- Patent number
- US09139584B2
Reaction notes
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