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

HRID 401103Notes

Reaction equation

HRID 401103 reaction equation
N[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:13][C:12](=[O:14])[NH:11][CH:10]([C:15]3[CH:20]=[C:19]([N+]([O-])=O)C(O)=C(OCC)[CH:16]=3)[C:9]=2[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[CH:4][CH:3]=1.[C:34]1([C:40](=[O:48])CC2C=CC=CC=2)C=CC=CC=1.N[C:50](N)=[O:51].Cl.[CH2:54]([OH:56])[CH3:55]>CCOC(C)=O>[OH:56][C:54]1[CH:16]=[C:15]([CH:10]2[C:9]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[C:8]([C:5]3[CH:4]=[CH:3][CH:2]=[CH:7][CH:6]=3)[NH:13][C:12](=[O:14])[NH:11]2)[CH:20]=[CH:19][C:55]=1[C:50]([O:48][CH2:40][CH3:34])=[O:51]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 702EthanolHCID 1176UreaHCID 99482-PhenylacetophenoneHCID 513483616-(4-aminophenyl)-4-(3-ethoxy-4-hydroxy-5-nitrophenyl)-5-phenyl-3,4-dihydropyrimidin-2(1H)-one2×

Product 1

HCID 67061122Ethyl 2-hydroxy-4-(2-oxo-5,6-diphenyl-1,2,3,4-tetrahydropyrimidin-4-yl)benzoateYield 69.5%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of methyl 4-formyl-2-hydroxybenzoate (Intermediate 84) (125 mg, 0.69 mmol), 1,2-diphenylethanone (136.2 mg, 0.69 mmol), urea (124.8 mg, 2.08 mmol), concentrated hydrochloric acid (1.0 mL) in ethanol (5 mL) was heated at 90° C. for 40 hours. Followed standard aqueous/EtOAc workup procedure to give crude ethyl 2-hydroxy-4-(2-oxo-5,6-diphenyl-1,2,3,4-tetrahydropyrimidin-4-yl)benzoate (200 mg, yield 69.5%). To a solution of this crude material (200 mg, 0.483 mmol) in water (5 mL) and ethanol (5 mL) was added sodium hydroxide (38.64 mg, 0.966 mmol) at 0° C. The mixture was stirred at 30° C. for 4 hours, then partitioned between ethyl acetate (70 mL) and water (50 mL). The organic layer was discarded and the aqueous layer was adjusted to pH=3 by hydrochloric acid (2M). Followed a standard aqueous/EtOAc workup. The residue was purified by preparative HPLC to give Compound 138 (31.3 mg, yield 16.8%). 1HNMR (DMSO-d6 400 MHz): δ 11.27 (s, 1H), 8.71 (s, 1H), 7.77 (d, J=8.0 Hz, 1H), 7.26 (s, 1H), 7.25-7.19 (m, 5H), 7.03-6.99 (m, 3H), 6.93 (d, J=8.0 Hz, 1H), 6.87 (s, 1H), 6.81 (d, J=6.4 Hz, 2H), 5.16 (d, J=2.8 Hz, 1H); MS (ESI): m/z 387.0 [M+H]+.

Sources & evidence

ORD record
ord-300078041002495fbd14ade7d8042513
Source dataset
uspto-grants-2014_06
Patent number
US08741915B2

Reaction notes

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