1,3-dimethylurea

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1,2-diphenylethanone (300 mg, 1.53 mmol), 3-ethoxy-4-hydroxy-5-nitrobenzaldehyde (324 mg, 1.53 mmol), and 1,3-dimethylurea (174 mg, 1.98 mmol) in DMF (5 mL) was added TMSCl (1.0 g, 9.12 mmol), and the reaction mixture was stirred at room temperature overnight under nitrogen. LCMS showed that about 30% of starting materials were consumed. H2O (10 mL) was added to quench the reaction, and the aqueous layer was extracted with EtOAc (30 mL×3). The combined organic layer was washed with brine (20 mL), dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography (PE: EtOAc=1:2) and preparative HPLC to afford Compound 41 as a yellow solid (82 mg, yield: 11.6%). 1H NMR (DMSO-d6 400 MHz): δ 10.40 (s, 1H), 7.50 (s, 1H), 7.30 (d, J=6.0 Hz, 3H), 7.25 (d, J=8.0 Hz, 3H), 7.00 (d, J=6.8 Hz, 3H), 6.75 (d, J=6.4 Hz, 2H), 5.11 (s, 1H), 4.00-4.17 (m, 2H), 2.82 (s, 3H), 2.75 (s, 3H), 1.33 (t, J=6.8 Hz, 3H); MS (ESI): m/z 460.1 [M+1]+. were consumed H2O (10 mL) was added to quench the reaction the aqueous layer was extracted with EtOAc (30 mL×3) The combined organic layer was washed with brine (20 mL) dried over Na2SO4 filtered concentrated The residue was purified by column chromatography (PE: EtOAc=1:2) and preparative HPLC

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 44 g of N,N'-dimethylurea were dissolved in 150 g of o-dichlorobenzene and reacted with 72 g of dimethylmaleate for 2 hours at 180°-185° C after the addition of 25 g of cresol. The solvent was removed from this reaction mixture and the residue was fractionated under vacuum, 85 g (= 85% of the theory) of the desired product distilling over at 0.07 Torr and 128° C. A purified product melting at 49.5° C could be obtained by dissolving the crude product in chloroform and reprecipitating it with ether. The structure of the purified product was confirmed by IR and NMR spectra and by elementary analysis. The solvent was removed from this reaction mixture distilling over at 0.07 Torr and 128° C

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Cyanoacetyldimethylurea is prepared in analogy to Example 1. Instead of dibenzylurea, dimethylurea is employed. The product is worked up by stripping off the acetic anhydride/acetic acid mixture on a rotary evaporator under reduced pressure. The residue obtained in this way is recrystallized from water. on a rotary evaporator under reduced pressure The residue obtained in this way is recrystallized from water

Conditions: temp:165.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 19.1 parts of N-phenyl maleic acid monoamide 8.8 parts of N,N'-dimethyl urea and 100 parts of cresol is stirred for 2.5 hours at 165° C. The solvent is distilled off in vacuo and the residue fractionated. An oily liquid distills over at a boiling point of from 220° to 223° C./0.1 Torr and solidifies after a while. Recrystallisation from n-propanol gives the compound confirmed by IR- (bands characteristic of hydantoins at 1705 and 1765 cm-1 and of amide at 1690 cm-1) and NMR-spectra. The solvent is distilled off in vacuo An oily liquid distills over at a boiling point of from 220° to 223° C./0.1 Torr Recrystallisation from n-propanol gives the compound

Conditions: temp:165.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 19.1 parts of N-phenyl maleic acid monoamide 8.8 parts of N,N'-dimethyl urea and 100 parts of cresol is stirred for 2.5 hours at 165° C. The solvent is distilled off in vacuo and the residue fractionated. An oily liquid distills over at a boiling point of from 220° to 223° C./0.1 Torr and solidifies after a while. Recrystallisation from n-propanol gives the compound confirmed by IR- (bands characteristic of hydantoins at 1705 and 1765 cm-1 and of amide at 1690 cm-1) and NMR-spectra. The solvent is distilled off in vacuo An oily liquid distills over at a boiling point of from 220° to 223° C./0.1 Torr Recrystallisation from n-propanol gives the compound

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 17.3 parts of N-phenyl maleic imide and 8.8 parts of N,N'-dimethyl urea in 100 parts of cresol is stirred for three hours at 190° C. The solvent is distilled off in vacuo and the residue fractionated. The oily liquid which distills at a boiling point of 220° C./0.1 Torr solidifies after a while and may be recrystallised from n-propanol (Mp. 114°-115° C.). IR and NMR-spectra confirm the assumed compound. The solvent is distilled off in vacuo The oily liquid which distills at a boiling point of 220° C./0.1 Torr may be recrystallised from n-propanol (Mp. 114°-115° C.)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 17.3 parts of N-phenyl maleic imide and 8.8 parts of N,N'-dimethyl urea in 100 parts of cresol is stirred for three hours at 190° C. The solvent is distilled off in vacuo and the residue fractionated. The oily liquid which distills at a boiling point of 220° C./0.1 Torr solidifies after a while and may be recrystallised from n-propanol (Mp. 114°-115° C.). IR and NMR-spectra confirm the assumed compound. The solvent is distilled off in vacuo The oily liquid which distills at a boiling point of 220° C./0.1 Torr may be recrystallised from n-propanol (Mp. 114°-115° C.)

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-amino 4-fluoro benzoic acid (2.5 g, 16.13 mmol) and 1,3 dimethyl urea (5.85 g, 66.5 mmol) was heated at 150° C. for 24 hours. The reaction was diluted with water, filtered and extracted twice with ethyl acetate. The organic extracts were dried over magnesium sulfate and concentrated at reduced pressure. Chromatography on silica gel with ethyl acetate in hexanes (0-50%) gave the title compound as a waxy solid (670 mg, 25%) filtered extracted twice with ethyl acetate The organic extracts were dried over magnesium sulfate concentrated at reduced pressure

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-amino 4-fluoro benzoic acid (2.5 g, 16.13 mmol) and 1,3 dimethyl urea (5.85 g, 66.5 mmol) was heated at 150° C. for 24 hours. The reaction was diluted with water, filtered and extracted twice with ethyl acetate. The organic extracts were dried over magnesium sulfate and concentrated at reduced pressure. Chromatography on silica gel with ethyl acetate in hexanes (0-50%) gave the title compound as a waxy solid (670 mg, 25%) filtered extracted twice with ethyl acetate The organic extracts were dried over magnesium sulfate concentrated at reduced pressure