Tetrahydrofuran → HCID 25227124, compound
Reaction equation
Cl[C:2]1[N:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4]1[CH:16]=[C:15]([F:17])[CH:14]=[CH:13][C:5]=1[N:6]=[C:7]2Cl.[F:18][C:19]([F:26])([F:25])[C@@H:20]([NH2:24])[CH:21]([CH3:23])[CH3:22].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C1C[O:40]CC1>>[F:17][C:15]1[CH:14]=[CH:13][C:5]2[N:6]=[C:7]([NH:24][C@H:20]([C:19]([F:26])([F:25])[F:18])[CH:21]([CH3:23])[CH3:22])[C:8]3[CH:9]=[CH:10][NH:11][C:2](=[O:40])[C:3]=3[C:4]=2[CH:16]=1Participants
5
Conditions
- Temperature
- 85 °C
Procedure
To a solution of 1,5-dichloro-9-fluorobenzo[c]-2,6-naphthyridine (50 mg, 0.19 mmol) (Example 1, Step 5) in THF (3 mL), were added (2S)-1,1,1-trifluoro-3-methylbutan-2-amine (26 mg, 0.19 mmol) and lithium bis(trimethylsilyl)amide (0.56 mL, 1.0 M in THF, 0.56 mmol). The solution was heated to 85° C. for 1 hr then cooled to room temperature. The reaction mixture was quenched with methanol and concentrated under reduced pressure. The crude mixture was taken up in THF (1 mL) and HCl (1 mL, 6 N) and heated to 85° C. for 1.5 hr. The solution was cooled and worked up with EtOAc and saturated NaHCO3. The organic layers were combined, dried over MgSO4, filtered, and concentrated to afford the title product.
Workup
- temperaturethen cooled to room temperature
- customThe reaction mixture was quenched with methanol
- concentrationconcentrated under reduced pressure
- temperatureHCl (1 mL, 6 N) and heated to 85° C. for 1.5 hr
- temperatureThe solution was cooled
- dry with materialdried over MgSO4
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-6bb31a79af52489f8d4fa5e12f06d6b7
- Source dataset
- uspto-grants-2013_01
- Patent number
- US08349865B2
Reaction notes
Loading…