Diisopropylethylamine → (R)-3-{4-[2-(2-o-tolylamino-3H-benzimidazol-5-yl)acetylamino]phenyl}butanoic acid dihydrate

A solution of 2-(2-o-tolylamino)benzimidazole-5-acetic acid hydrochloride (200 mg, Reference Example 7), ethyl (R)-3-(4-aminophenyl)butanoate (147 mg, Reference Example 1) and O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (300 mg) in dimethylformamide (5 mL) was treated with diisopropylethylamine (470 mg). After stirring at room temperature for 2 hours the reaction mixture was partitioned between ethyl acetate and dilute aqueous acetic acid. The layers were separated and the organic layer was washed with 5% aqueous sodium bicarbonate solution, then dried, and then evaporated. The yellow semi-solid residue (120 mg) was dissolved in ethanol (5 mL) and the solution was treated with aqueous lithium hydroxide solution (2 mL, 2M). After standing at room temperature for 2 hours the mixture was acidified by addition of dilute acetic acid. The resulting white solid was collected by filtration, and sucked dry in the filter funnel to give the title compound (42 mg) as a white amorphous solid. LC-MS: RT=2.29 minutes (100% by ELSD); MS (ES+), 443 (MH+).

1. customwas partitioned between ethyl acetate and dilute aqueous acetic acid
2. customThe layers were separated
3. washthe organic layer was washed with 5% aqueous sodium bicarbonate solution
4. customdried
5. customevaporated
6. dissolutionThe yellow semi-solid residue (120 mg) was dissolved in ethanol (5 mL)
7. additionthe solution was treated with aqueous lithium hydroxide solution (2 mL, 2M)
8. waitAfter standing at room temperature for 2 hours
9. additionthe mixture was acidified by addition of dilute acetic acid
10. filtrationThe resulting white solid was collected by filtration
11. customsucked dry in the filter funnel

ORD-Eintrag

ord-922ed1de3b0c42a683eedb6b50a974b5

Quelldatensatz

uspto-grants-2003_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06593354B2