Methanol → Methyl 6-aminopyrimidine-4-carboxylate
Reaction equation
Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH2:8])[CH:3]=1.CCN(CC)CC.[CH3:16][OH:17].CN([CH:21]=[O:22])C>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:8][C:4]1[N:5]=[CH:6][N:7]=[C:2]([C:16]([O:22][CH3:21])=[O:17])[CH:3]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 100 °C
Procedure
A mixture of 6-chloropyrimidin-4-amine (10.0 g, 77.2 mmol), PdCl2(dppf) (6.0 g, 8.2 mmol), Et3N (30 mL), MeOH (30 mL) in DMF (100 mL) was heated 100° C. for 24 h under 20 atm CO (g) atmosphere. The solvents were removed under reduced pressure, and the residue was partitioned between water (100 mL) and ethyl acetate (100 mL). The aqueous layer was extracted with ethyl acetate (100 mL) three times. The combined organic phase was dried over Na2SO4 and concentrated. The resulting residue was purified by silica gel column chromatography (0-10% MeOH/DCM) to give the desired product as a gray solid (5.0 g, 42% yield). 1H-NMR (500 MHz, DMSO-d6): δ 8.44 (d, J=0.5 Hz, 1H), 7.27 (s, 2H), 7.03 (d, J=1.5 Hz, 1H), 3.84 (s, 3H). LCMS (ESI) m/z: 154.1 [M+H+].
Workup
- customThe solvents were removed under reduced pressure
- customthe residue was partitioned between water (100 mL) and ethyl acetate (100 mL)
- extractionThe aqueous layer was extracted with ethyl acetate (100 mL) three times
- dry with materialThe combined organic phase was dried over Na2SO4
- concentrationconcentrated
- customThe resulting residue was purified by silica gel column chromatography (0-10% MeOH/DCM)
Sources & evidence
- ORD record
- ord-d2843c779f624d94ad41f57010a4cc5f
- Source dataset
- uspto-grants-2014_04
- Patent number
- US08697708B2
Reaction notes
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