Cesium carbonate → HCID 59286574, compound
Reaction equation
[F:1][C:2]1[C:7]([C:8]2[N:13]=[CH:12][N:11]=[C:10]([NH:14][C:15]([NH:17][CH2:18][C@@:19]3([OH:27])[CH:24]4[CH2:25][CH2:26][N:21]([CH2:22][CH2:23]4)[CH2:20]3)=S)[CH:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].CC(C)N=C=NC(C)C>CN(C)C=O.C(OCC)(=O)C>[OH-:27].[NH4+:3].[F:1][C:2]1[C:7]([C:8]2[N:13]=[CH:12][N:11]=[C:10]([NH:14][C:15]3[O:27][C@:19]4([CH2:18][N:17]=3)[CH:24]3[CH2:25][CH2:26][N:21]([CH2:22][CH2:23]3)[CH2:20]4)[CH:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1Participants
Procedure
To suspension of (S)-1-(6-(2-fluoropyridin-3-yl)pyrimidin-4-yl)-3-((3-hydroxyquinuclidin-3-yl)methyl)thiourea (0.2 g, 0.515 mmol) in N,N-dimethylformamide (20 mL) was added Cs2CO3 (0.168 g, 0.515 mmol) and DIC (0.241 mL, 1.545 mmol). The suspension was stirred at room temperature for 18 h, then at 60° C. for 3 h. The mixture was concentrated and the residue was purified on silica gel using 2-7% 9.5:0.5 methanol:ammonium hydroxide in ethyl acetate to afford (R)—N-(6-(2-fluoropyridin-3-yl)pyrimidin-4-yl)-4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octan]-2-amine as a pale yellow solid (0.029 g, 0.081 mmol, 16%). 1H NMR (400 MHz, MeOD) δ ppm 8.83 (1H, d, J=1.26 Hz), 8.55 (1H, ddd, J=9.76, 7.62, 2.01 Hz), 8.29 (1H, dt, J=3.02, 1.51 Hz), 7.46 (1H, ddd, J=7.37, 5.10, 1.89 Hz), 7.33 (1H, s), 4.06 (1H, d, J=10.32 Hz), 3.76 (1H, d, J=10.32 Hz), 3.25 (1H, s), 3.09-3.19 (1H, m), 2.95 (2H, t, J=7.68 Hz), 2.74-2.91 (2H, m), 2.04-2.26 (2H, m), 1.55-1.87 (3H, m). MS (LC/MS) R.T.=1.24; [M+H]+=355.28.
Workup
- waitat 60° C. for 3 h
- concentrationThe mixture was concentrated
- customthe residue was purified on silica gel using 2-7% 9.5:0.5 methanol
Sources & evidence
- ORD record
- ord-82642162e803494eab90226d0a1e46fd
- Source dataset
- uspto-grants-2012_11
- Patent number
- US08309577B2
Reaction notes
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