Hydrochloric Acid → Ethyl 2-chloro-4-(2-oxo-5,6-diphenyl-1,2,3,4-tetrahydropyrimidin-4-yl)benzoate
Reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]([CH:12]=O)[CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[C:14]1([C:20](=O)[CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[NH2:29][C:30]([NH2:32])=[O:31].Cl.[CH2:34](O)C>CCOC(C)=O>[Cl:1][C:2]1[CH:11]=[C:10]([CH:12]2[C:21]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[C:20]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[NH:32][C:30](=[O:31])[NH:29]2)[CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH2:7][CH3:34])=[O:5]Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 95 °C
Procedure
To a mixture of methyl 2-chloro-4-formylbenzoate (Intermediate 75) (210 mg, 1.1 mmol), 1,2-diphenylethanone (208 mg, 1.1 mmol), urea (191 mg, 3.2 mmol) and conc. HCl (0.5 mL) in ethanol (2 mL) was refluxed at 95° C. for 30 hours. A standard aqueous/EtOAc workup procedure was followed to give crude ethyl 2-chloro-4-(2-oxo-5,6-diphenyl-1,2,3,4-tetrahydropyrimidin-4-yl)benzoate (360 mg). This was taken up in water (2.5 mL) and ethanol (2.5 mL) and sodium hydroxide (67 mg, 1.7 mmol) was added at 30° C. The resulting mixture was stirred at 40° C. for 6 hours. HCl (2 N) was added until pH=3. A standard aqueous/EtOAc workup procedure was followed and crude was purified by prep-HPLC (0.1% TFA as additive) to give Compound 145 (57.3 mg, yield 17%). 1H NMR (DMSO 400 MHz): δ 13.37 (brs, 1H), 8.76 (s, 1H), 7.78 (d, J=7.6 Hz, 1H), 7.63 (s, 1H), 7.43-7.36 (m, 2H), 7.26-7.19 (m, 5H), 7.05-6.98 (m, 3H), 6.81 (d, J=6.4 Hz, 2H), 5.28 (d, J=2.4 Hz, 1H), MS (ESI): m/z 404.9 [M+H]+.
Sources & evidence
- ORD record
- ord-82169096bd96492c902688bcd2853323
- Source dataset
- uspto-grants-2016_03
- Patent number
- US09283229B2
Reaction notes
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