1,3-oxazolidine

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:

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: BM 2: 500 parts of an epoxy resin based on Bisphenol A and epichlorohydrin (epoxy equivalent weight about 500) are dissolved in 214 parts propyleneglycol monomethylether and reacted at 110° C. with 83 parts of a semiester of phthalic acid anhydride and 2 ethylhexanol, in the presence of 0.5 parts of triethylamine as catalyst, to an acid value of below 3 mg KOH/g. Then, 120 parts of an NH-functional oxazolidine of aminoethylethanolamine, 2-ethylhexylacrylate and formaldehyde, and 26 parts diethylaminopropylamine are added and the batch is reacted at 80° C. to an epoxy value of practically zero. The batch is diluted with 200 parts propyleneglycol monomethylether. 70 parts (resin solids) of this oxazolidine modified epoxy resin amine adduct are homogenized for 30 minutes at 50° C. with 30 parts based on resin solids of a crosslinking component obtained through reaction of 1 mole of a toluylene diisocyanate semi-blocked with 2-ethylhexanol and 0.33 moles triethanolamine. The reaction is carried out in a 70% solution of diethyleneglycol dimethylether, at 50 to 60° C. until all isocyanate groups have reacted.

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

Procedure: Acetyl chloride (460 mL, 6470 mmol) was added via addition funnel to methanol (1080 mL) at 0° C. A solution of 1 (18.3 g, 71.8 mmol) in methanol (10 mL) was added and the reaction mixture refluxed for 3 hours. Evaporation of the volatiles in vacuo produced a white solid which was dissolved in dioxane (150 mL) and H2O (50 mL). NaHCO3 (12.1 g, 144 mmol) and benzyl chloroformate (20.5 mL, 144 mmol) were added, and the reaction mixture was stirred overnight. The reaction mixture was extracted with EtOAc (3×), and the combined organic phases were washed with brine, dried over MgSO4, filtered and concentrated. Column chromatography (SiO2, EtOAc—hexane gradient elution) afforded 2 (12.25 g, 58%) as a colorless oil: [α]RTD−0.4° (c2.1, CHCl3); 1H NMR (300 MHz, CDCl3) δ7.37-7.29 (m, 5H), 5.79 (br s, 1H), 5.68-5.52 (m, 1H), 5.15-5.01 (m, 4H), 4.18-4.07 (m, 1H), 3.88-3.76 (m, 1H), 3.75 (s, 3H), 3.51 (br s, 1H), 2.78 (dd, J=13.8, 7.8 Hz, 1H), 2.52 (dd, J=14.1, 7.2 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ172.25, 155.24, 135.95, 131.02, 128.36, 128.04, 127.90, 119.91, 66.69, 65.08, 64.93, 52.73, 36.73; IR (film) νmax 3407, 1724 cm−1. the reaction mixture refluxed for 3 hours Evaporation of the volatiles in vacuo produced a white solid which The reaction mixture was extracted with EtOAc (3×) the combined organic phases were washed with brine dried over MgSO4 filtered concentrated Column chromatography (SiO2, EtOAc—hexane gradient elution)

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: 2,3-Dichloro-4-methylaniline was converted to the 2,3-dichloro-4-methylformanilide according to Method A3a, Step 1. The formanilide was converted to 2,3-dichloro-4-methylphenyl isocyanide dichloride according to Method A3a, Step 2. 1-Hydroxymethylcyclopentanamine HCl salt was synthesized according to Method B1c. The 2-hydroxyethylamine was converted to 13-aza-6-oxadispiro[4.2.4.1]tridecane according to Method B4d, Step 1. The oxazolidine was reductively opened according to Method B4d, Step 2 to give 1-(cyclopentylamino)-1-(hydroxymethyl)cyclopentane. The substituted 2-hydroxyethylamine was converted to 1-(cyclopentylamino)-1-(thioacetylmethyl)cyclopentane according to Method C6c, Step 1. The thioacetate was hydrolyzed according to Method C6c, Step 2 to give 1-(cyclopentylamino)-1-(thiomethyl)cyclopentane. The 2-thioethylamine was reacted with 2,3-dichloro-4-methylphenyl isocyanide dichloride according to Method C6c to afford 2-(2,3-dichloro-4-methylphenylimino)-1-cyclopentyl-3-thia-1-azaspiro[4.4]nonane.

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

Procedure: 2,3-Dichloro-4-methylaniline was converted to the 2,3-dichloro-4-methylformanilide according to Method A3a, Step 1. The formanilide was converted to 2,3-dichloro-4-methylphenyl isocyanide dichloride according to Method A3a, Step 2. 1-Hydroxymethylcyclopentanamine HCl salt was synthesized according to Method B1c. The 2-hydroxyethylamine was converted to 13-aza-6-oxadispiro[4.2.4.1]tridecane according to Method B4d, Step 1. The oxazolidine was reductively opened according to Method B4d, Step 2 to give 1-(cyclopentylamino)-1-(hydroxymethyl)cyclopentane. The substituted 2-hydroxyethylamine was converted to 1-(cyclopentylamino)-1-(thioacetylmethyl)cyclopentane according to Method C6c, Step 1. The thioacetate was hydrolyzed according to Method C6c, Step 2 to give 1-(cyclopentylamino)-1-(thiomethyl)cyclopentane. The 2-thioethylamine was reacted with 2,3-dichloro-4-methylphenyl isocyanide dichloride according to Method C6c to afford 2-(2,3-dichloro-4-methylphenylimino)-1-cyclopentyl-3-thia-1-azaspiro[4.4]nonane.

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

Procedure: 3-Chloro-2-methylaniline was converted to the 3-chloro-2-methylformanilide according to Method A3a, Step 1. The formanilide was converted to 3-chloro-2-methylphenyl isocyanide dichloride according to Method A3a, Step 2. 1-Hydroxymethylcyclopentanamine HCl salt was synthesized according to Method B1c. The 2-hydroxyethylamine was converted to 13-aza-6-oxadispiro[4.2.4. 1]tridecane according to Method B4d, Step 1. The oxazolidine was reductively opened according to Method B4d, Step 2 to give 1-(cyclopentylamino)-1-(hydroxymethyl)cyclopentane. The substituted 2-hydroxyethylamine was converted to 1-(cyclopentylamino)-1-(thioacetylmethyl)cyclopentane according to Method C6c, Step 1. The thioacetate was hydrolyzed according to Method C6c, Step 2 to give 1-(cyclopentylamino)-1-(thiomethyl)cyclopentane. The 2-thioethylamine was reacted with 3-chloro-2-methylphenyl isocyanide dichloride according to Method C6c to afford 2-(3-chloro-2-methylphenylimino)-1-cyclopentyl-3-thia-1-azaspiro[4.4]nonane.