N,N-Dimethylaniline → 4-Chloro-6-(tetrahydro-furan-3-yl)-pyrimidin-2-ylamine
Reaction equation
[NH2:1][C:2]1[NH:7][C:6](=O)[CH:5]=[C:4]([CH:9]2[CH2:13][CH2:12][O:11][CH2:10]2)[N:3]=1.CN(C)C1C=CC=CC=1.P(Cl)(Cl)([Cl:25])=O>[Cl-].C([N+](CC)(CC)CC)C.C(#N)C>[Cl:25][C:6]1[CH:5]=[C:4]([CH:9]2[CH2:13][CH2:12][O:11][CH2:10]2)[N:3]=[C:2]([NH2:1])[N:7]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 110 °C
Procedure
A suspension of 2-amino-6-(tetrahydro-furan-3-yl)-3H-pyrimidin-4-one (1.5 g, 8.28 mmol), tetraethyl ammonium chloride (2.7 g 16.3 mmol) and dimethylaniline (1.4 mL, 11.1 mmol) in acetonitrile (15 mL) was treated with phosphorous oxychloride (2.4 mL, 26.2 mmol) and heated at 110° C. for 20 min. The resulting solution was cooled to rt and concentrated to minimum volume and pipetted onto ice chips. The aqueous portion was extracted with EtOAc (3×50 mL). The combined organic layers were basified with satd. aq. NaHCO3 solution to pH˜7. The organic portion was separated, dried, and concentrated. The crude material was chromatographed (MeOH/CH2Cl2) to yield 680 mg (42%) of product as a light orange foam. 1H NMR (CDCl3): 6.59 (s, 1H), 5.16 (br s, 2H), 4.00-4.10 (m, 2H), 3.85-3.91 (m, 2H), 3.28-3.35 (m, 1H), 2.25-2.34 (m, 1H), 2.08-2.18 (m, 1H).
Workup
- temperatureThe resulting solution was cooled to rt
- concentrationconcentrated to minimum volume
- extractionThe aqueous portion was extracted with EtOAc (3×50 mL)
- customThe organic portion was separated
- customdried
- concentrationconcentrated
- customThe crude material was chromatographed (MeOH/CH2Cl2)
Sources & evidence
- ORD record
- ord-72e0d3eed2bf47ad847491e957717d56
- Source dataset
- uspto-grants-2011_04
- Patent number
- US07923451B2
Reaction notes
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