Pyridine → HCID 89779425, compound
Reaction equation
[C:1]([NH:9][C:10]([NH:12][C@:13]1([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[F:31])[C@H:17]([CH:18]([OH:23])[C:19]([F:22])([F:21])[F:20])[C@@H:16]([CH3:24])[O:15][CH2:14]1)=S)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CC=CC=1.S(OS(C(F)(F)F)(=O)=O)(C(F)(F)F)(=O)=O>>[F:31][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=1[C@:13]12[CH2:14][O:15][C@H:16]([CH3:24])[C@H:17]1[C@@H:18]([C:19]([F:22])([F:21])[F:20])[O:23][C:10]([NH:9][C:1](=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[N:12]2Participants
4
Conditions
- Temperature
- 0 °C
Procedure
1-Benzoyl-3-[(3S,4R,5R)-3-(2-fluoro-phenyl)-5-methyl-4-(2,2,2-trifluoro-1-hydroxy-ethyl)-tetrahydro-furan-3-yl]-thiourea (Preparation Example 30-(5)) (300 mg, 0.65 mmol) was dissolved in pyridine (1.39 g, 17.61 mmol). The reaction mixture was cooled to 0° C. Triflic anhydride (250 mg, 0.88 mmol) was added drop wise over 30 min, keeping temperature below 10° C. After 1 h, the reaction was concentrated then HCl 1M (50 ml) was added followed by extraction with DCM (2×50 ml). The organic phase was dried on MgSO4 and concentrated. The resulting mixture was purified by flash chromatography (Hexane/EtOAc 10-50%). 278 mg (93% yield) of the title compound (85%) and its isomer (15%) were isolated as a mixture.
Workup
- customtemperature below 10° C
- concentrationthe reaction was concentrated
- additionHCl 1M (50 ml) was added
- extractionfollowed by extraction with DCM (2×50 ml)
- customThe organic phase was dried on MgSO4
- concentrationconcentrated
- customThe resulting mixture was purified by flash chromatography (Hexane/EtOAc 10-50%)
Sources & evidence
- ORD record
- ord-69fc4457ffc849be99791f571b22781b
- Source dataset
- uspto-grants-2015_07
- Patent number
- US09079914B2
Reaction notes
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