Aniline → 4-methoxy-N-phenylpyrimidin-2-amine
Reaction equation
Cl[C:2]1[N:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][N:3]=1.[NH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.CCN(C(C)C)C(C)C>CC(O)C>[CH3:9][O:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[N:7]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 100 °C
Procedure
A sealed tube was charged with 2-chloro-4-methoxypyrimidine (1.00 g, 6.92 mmol) in 2-propanol (5 mL). Aniline (0.757 ml, 8.30 mmol) and DIEA (1.45 ml, 8.30 mmol) were added and the reaction mixture was heated at 100° C. until the reaction was complete by HPLC. The reaction mixture was cooled to room temperature. The resulting thick suspension was filtered, washed with ethanol, collected and dried under vacuum to yield the desired product (0.164 g) as a white solid. The filtrate was concentrated and then partitioned between EtOAc and saturated aqueous NaCl. The phases were separated, and the aqueous phase was re-extracted with EtOAc (1×). The combined organic layers were dried (Na2SO4), filtered and concentrated to yield a yellow solid. The crude product was purified by flash column chromatography, eluting with 25:1 dichloromethane/EtOAc. The desired product (0.548 g) was obtained as a white solid which was combined with the filtered product to yield 0.712 g (51%) total desired product. 1H-NMR (400 MHz, DMSO-d6) δ 9.51 (s, 1H), 8.20 (d, 1H), 7.77 (d, 2H), 7.27 (t, 2H), 6.94 (t, 1H), 6.28 (d, 1H), 3.91 (s, 3H). LRMS (ESI pos) m/e 202 (M+1).
Workup
- temperatureThe reaction mixture was cooled to room temperature
- filtrationThe resulting thick suspension was filtered
- washwashed with ethanol
- customcollected
- customdried under vacuum
Sources & evidence
- ORD record
- ord-38930fbfabbf42c9b4b17ef41694f26f
- Source dataset
- uspto-grants-2011_08
- Patent number
- US08003662B2
Reaction notes
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