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

HRID 270246Notes

Reaction equation

HRID 270246 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([NH:7]C=O)[CH:4]=[C:3]1[C:10]([Cl:12])=[O:11].C(N(C(C)C)CC)(C)C.[NH2:22][CH2:23][CH2:24][C:25]#[N:26].Cl>O1CCCC1.CO>[ClH:12].[CH3:1][N:2]1[CH:6]=[C:5]([NH2:7])[CH:4]=[C:3]1[C:10]([NH:26][CH2:25][CH2:24][C:23]#[N:22])=[O:11]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 16473-AminopropionitrileHCID 81531DiisopropylethylamineHCID 118162971-Methyl-4-formylamino-2-pyrrolecarbonyl chloride

Product 1

HCID 179812173-(1-Methyl-4-amino-2-pyrrolecarboxamido)propionitrile hydrochloride

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

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.

Workup

  1. customThe reaction mixture is evaporated under vacuum
  2. washthe resulting crude product is washed with water several times
  3. customdried
  4. customto yield crude 3-(1-methyl-4-formylamino-2-carboxamido)propionitrile
  5. customthe methanol is evaporated
  6. customthe resulting crude product is crystallized from isopropanol/ethyl acetate

Sources & evidence

ORD record
ord-284a6939e1c34b95b888b59b403ba827
Source dataset
uspto-grants-2008_11
Patent number
US07449547B2

Reaction notes

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