1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → HCID 54450099, compound

Half of the crude N-((1R)-1-{N-[(1R)-1-(((dimethylcarbamoyl)methoxy)methyl)-2-phenylethyl]-N-methylcarbamoyl}-2-{2-naphthyl}ethyl)-N-methylcarbamic acid tert-butylester (132 mg, 0.23 mmol) was dissolved in a mixture of dichloromethane and trifluoroacetic acid 1:1 (2 ml) and stirred for 10 min. The mixture was concentrated by a stream of nitrogen and the resulting oil was redissolved in 1 ml 1N hydrochloric acid, diluted with water to a volume of 50 ml and lyophilized. This lyophilized product was dissolved in dichloromethane (5 ml) and diisopropylethyl amine (171 μl) was added. To this mixture was added a solution in dichloromethane (5 ml) of 3-tert-butyloxycarbonylaminomethylbenzoic acid (503 mg, 2.0 mmol) which immediately before had been converted to the symmetrical anhydride by stirring with N-ethyl-N'-(3-dimethylaminopropyl)-carbodiimide hydrochloride (191.6 mg, 1.0 mmol) for 15 min. The reaction mixture was then concentrated to an oil and redissolved in ethyl acetate (25 ml). This mixture was extracted sequentially with 5% aqueous sodium hydrogencarbonate (50 ml), 5% aqueous potassium hydrogen-sulfate (50 ml) and water (50 ml) and the organic phase was dried (sodium sulfate) and concentrated by a stream of nitrogen to dryness. This product was dissolved in a mixture of dichloromethane and trifluoroacetic acid 1:1 (4 ml). After 10 min the mixture was concentrated by a stream of nitrogen and the resulting oil was redissolved in 5 ml 70% acetonitrile/0.1% trifluoroacetic acid and diluted with water to a volume of 50 ml. The crude product of the title compound was then purified by semipreparative HPLC in four runs on a 25 mm×250 mm column packed with 7μ C-18 silica which was preequilibrated with 29% acetonitrile in 0.05M ammonium sulfate, which was adjusted to pH 2.5 with 4M sulfuric acid.

1. concentrationThe mixture was concentrated by a stream of nitrogen
2. dissolutionthe resulting oil was redissolved in 1 ml 1N hydrochloric acid
3. additiondiluted with water to a volume of 50 ml
4. dissolutionThis lyophilized product was dissolved in dichloromethane (5 ml)
5. additiondiisopropylethyl amine (171 μl) was added
6. concentrationThe reaction mixture was then concentrated to an oil
7. dissolutionredissolved in ethyl acetate (25 ml)
8. extractionThis mixture was extracted sequentially with 5% aqueous sodium hydrogencarbonate (50 ml), 5% aqueous potassium hydrogen-sulfate (50 ml) and water (50 ml)
9. dry with materialthe organic phase was dried (sodium sulfate)
10. concentrationconcentrated by a stream of nitrogen to dryness
11. dissolutionThis product was dissolved in a mixture of dichloromethane and trifluoroacetic acid 1:1 (4 ml)
12. concentrationAfter 10 min the mixture was concentrated by a stream of nitrogen
13. dissolutionthe resulting oil was redissolved in 5 ml 70% acetonitrile/0.1% trifluoroacetic acid
14. additiondiluted with water to a volume of 50 ml
15. customThe crude product of the title compound was then purified by semipreparative HPLC in four runs on a 25 mm×250 mm column

ORD record

ord-112d2f72ef934bcfa5e013ce70aa23c0

Source dataset

uspto-grants-2000_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06013658