Reaction equation
[CH:1]1([CH2:4][C:5](=O)/[C:6](/[C:11]2[CH:16]=[CH:15][N:14]=[C:13]([S:17][CH3:18])[N:12]=2)=[CH:7]\[N:8](C)[CH3:9])[CH2:3][CH2:2]1.C(O)(=O)C.C(N)=[NH:25].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH:1]1([CH2:4][C:5]2[C:6]([C:11]3[CH:16]=[CH:15][N:14]=[C:13]([S:17][CH3:18])[N:12]=3)=[CH:7][N:8]=[CH:9][N:25]=2)[CH2:3][CH2:2]1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
A solution of (3Z)-1-cyclopropyl-4-(dimethylamino)-3-[2-(methylsulfanyl)pyrimidin-4-yl]but-3-en-2-one (3) (200 mg, 0.721 mmol), formamidine acetate (75 mg, 0.721 mmol), and K2CO3 (299 mg, 2.163 mmol) in DMF (6 mL) was stirred at 120° C. for 30 minutes, followed by stifling at rt for 18 hours. The reaction was partitioned between water and EtOAc. The organic layer was separated, and the aqueous layer was back-extracted. The organic extracts were combined, washed with brine, dried over sodium sulfate, then concentrated in vacuo. The crude product was purified by Biotage™ silica gel chromatography [10 g SNAP column, 30% EtOAc/heptane to 100% EtOAc] to obtain the desired product as a white solid (62.5 mg, 29.4% yield). The desired product contained a small amount of an unknown by-product and was carried on to the next step without further purification. MS (ES+): m/z=259.3 (100) [MH+2]. HPLC: tR=1.77 minutes over 3 minutes. Purity: 87.5% [HPLC (LC/MS) at 220 nm].
Workup
- customThe reaction was partitioned between water and EtOAc
- customThe organic layer was separated
- extractionthe aqueous layer was back-extracted
- washwashed with brine
- dry with materialdried over sodium sulfate
- concentrationconcentrated in vacuo
- customThe crude product was purified by Biotage™ silica gel chromatography [10 g SNAP column, 30% EtOAc/heptane to 100% EtOAc]
Sources & evidence
- ORD record
- ord-6a85f3ae292b40f993c5cd848596471f
- Source dataset
- uspto-grants-2014_12
- Patent number
- US08901147B2
Linked notes
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