Hydrochloric Acid → Ethyl 2-nitro-4-(2-oxo-5,6-diphenyl-1,2,3,4-tetrahydropyrimidin-4-yl)benzoate

HRID 2177989Notes

Reaction equation

HRID 2177989 reaction equation
[CH:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=[O:8])=[C:5]([N+:12]([O-:14])=[O:13])[CH:4]=1)=O.[C:15]1([C:21](=O)[CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[NH2:30][C:31]([NH2:33])=[O:32].Cl.[CH2:35](O)[CH3:36]>CCOC(C)=O>[N+:12]([C:5]1[CH:4]=[C:3]([CH:1]2[C:22]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[C:21]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[NH:33][C:31](=[O:32])[NH:30]2)[CH:11]=[CH:10][C:6]=1[C:7]([O:9][CH2:35][CH3:36])=[O:8])([O-:14])=[O:13]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 702EthanolHCID 1176UreaHCID 99482-PhenylacetophenoneHCID 203514394-Formyl-2-nitrobenzoic acid2×

Product 1

HCID 67061077Ethyl 2-nitro-4-(2-oxo-5,6-diphenyl-1,2,3,4-tetrahydropyrimidin-4-yl)benzoateYield 62.3%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
92 °C

Procedure

A mixture of 4-formyl-2-nitrobenzoic acid (Intermediate 73) (120 mg, 0.615 mmol), 1,2-diphenylethanone (120 mg, 0.615 mmol), urea (110 mg, 1.845 mmol), hydrochloric acid (0.5 mL) in ethanol (2 mL) was heated at 92° C. for 41 hours. A standard aqueous/EtOAc workup was followed to give crude ethyl 2-nitro-4-(2-oxo-5,6-diphenyl-1,2,3,4-tetrahydropyrimidin-4-yl)benzoate (170 mg, yield 62.3%). This was taken up in water (3 mL) and ethanol (3 mL) and sodium hydroxide (30.6 mg, 0.766 mmol) was added at 0° C., and the mixture was stirred at 28° C. for 5 hours. The reaction mixture was partitioned between water (30 mL) and ethyl acetate (70 mL). The organic layer was discarded and the aqueous layer was adjusted to pH=3 with hydrochloric acid (2 mol/L). Then the resulting mixture was extracted with ethyl acetate (30 mL×3). The organic layers were washed with brine (50 mL), dried over sodium sulfate and evaporated. Purified by preparative HPLC to give Compound 140 (37.1 mg, yield 23.3%). HNMR (DMSO-d6 300 MHz): δ 11.38 (s, 1H), 8.82 (s, 1H), 7.84 (d, J=7.8 Hz, 2H), 7.75-7.69 (m, 2H), 7.24 (m, 5H), 7.04-7.01 (m, 3H), 6.83 (d, J=7.8 Hz, 2H), 5.45 (d, J=2.7 Hz, 1H); MS (ESI): m/z 416.0 [M+H]+.

Sources & evidence

ORD record
ord-5eedaae4e0f6450da2ec8714bb904f68
Source dataset
uspto-grants-2015_06
Patent number
US09067893B2

Reaction notes

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