Potassium Hydroxide → N-(2-Fluoro-4-methylsulfanyl-phenyl)-2-pyrimidin-4-ylmethyl-malonamic acid methyl ester
Reaction equation
[CH3:1][O:2][C:3](=[O:17])[CH2:4][C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([S:14][CH3:15])=[CH:10][C:9]=1[F:16])=[O:6].Cl[CH2:19][C:20]1[CH:25]=[CH:24][N:23]=[CH:22][N:21]=1.[OH-].[K+]>>[CH3:1][O:2][C:3](=[O:17])[CH:4]([CH2:19][C:20]1[CH:25]=[CH:24][N:23]=[CH:22][N:21]=1)[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([S:14][CH3:15])=[CH:10][C:9]=1[F:16])=[O:6]Participants
Procedure
N-(2-Fluoro-4-methylsulfanyl-phenyl)-malonamic acid methyl ester (15.4 g, 59.9 mmol), 4-chloromethyl-pyrimidine (5.13 g, 39.9 mmol) and potassium hydroxide (3.36 g, 59.9 mmol) were dissolved in IMS (150 mL). The reaction mixture was stirred at room temperature for 16 hours then concentrated in vacuo. The resultant residue was dissolved in ethyl acetate (30 mL), washed with water (20 mL) and the aqueous fraction extracted twice with ethyl acetate (2×10 mL). The combined organic fractions were washed with brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0-100% ethyl acetate in cyclohexane) to yield the title compound as an off-white solid (4.9 g, 23%). LCMS (Method B): RT=3.02 min, M+H+=350.
Workup
- concentrationthen concentrated in vacuo
- dissolutionThe resultant residue was dissolved in ethyl acetate (30 mL)
- washwashed with water (20 mL)
- extractionthe aqueous fraction extracted twice with ethyl acetate (2×10 mL)
- washThe combined organic fractions were washed with brine
- dry with materialdried (MgSO4)
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-cb0088988a2a4639bdc66cf0a5e24d88
- Source dataset
- uspto-grants-2013_07
- Patent number
- US08486963B2
Reaction notes
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