Hydrochloric Acid → 3-(1-Methyl-4-amino-2-pyrrolecarboxamido)propionitrile hydrochloride

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Reaction Steps

To 1-methyl-4-formylamino-2-pyrrolecarbonyl chloride (II) (16.0 mmol) dissolved in 80 mL of tetrahydrofuran are added diisopropylethylamine (18 mmol) and 3-aminopropionitrile (18 mmol) with continuous stirring for 1 hour. The reaction mixture is evaporated under vacuum and the resulting crude product is washed with water several times and dried to yield crude 3-(1-methyl-4-formylamino-2-carboxamido)propionitrile. This is N-deformylated by treatment with 30 mL of a solution of hydrogen chloride in methanol for 1 hour, the methanol is evaporated and the resulting crude product is crystallized from isopropanol/ethyl acetate to furnish 3-(1-methyl-4-amino-2-pyrrolecarboxamido)propionitrile hydrochloride, whose analytical data are in agreement with the above mentioned literature. This compound is acylated with 1-methyl-4-formylamino-2-pyrrolecarbonyl chloride (II) as above and subjected to the Pinner reaction to yield the hydrochloride of 3-(1-methyl-4-(1-methyl-4-aminopyrrole-2-aminocarbonyl)pyrrole-2-carboxamido)propionamidine (Ib, n=0)) from which Distamycin is obtained as described in Example 4.

Provenance & Evidence