Water → 4-chloro-3-cyano-N-[(3S,4R)-3-ethoxypiperidin-4-yl]-5-methyl-1H-pyrrole-2-carboxamide

HRID 655767Notes

Reaction equation

HRID 655767 reaction equation
[Cl:1][C:2]1[C:3]([C:25]#[N:26])=[C:4]([C:8]([NH:10][C@@H:11]2[CH2:16][CH2:15][N:14](C(OCC)=O)[CH2:13][C@@H:12]2[O:22][CH2:23][CH3:24])=[O:9])[NH:5][C:6]=1[CH3:7].[OH-].[K+].O.NN.O>C(O)CO>[Cl:1][C:2]1[C:3]([C:25]#[N:26])=[C:4]([C:8]([NH:10][C@@H:11]2[CH2:16][CH2:15][NH:14][CH2:13][C@@H:12]2[O:22][CH2:23][CH3:24])=[O:9])[NH:5][C:6]=1[CH3:7]

Participants

6

Reactant 4

HCID 962WaterHCID 14797Potassium HydroxideHCID 24654Hydrazine hydrate (1:1)HCID 59402508HCID 59402508, compound2×

Product 1

HCID 594024474-chloro-3-cyano-N-[(3S,4R)-3-ethoxypiperidin-4-yl]-5-methyl-1H-pyrrole-2-carboxamideYield 55%

Reagents, catalysts & solvents 1

HCID 174Ethylene GlycolSolvent

Procedure

A solution of ethyl (3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-ethoxypiperidine-1-carboxylate (Intermediate 32, 1.5 g, 3.92 mmol), potassium hydroxide (1.54 g, 27.48 mmol), and hydrazine hydrate (1.38 mL, 27.48 mmol) in ethylene glycol (200 mL) was stirred for 60 h at 120° C. The reaction mixture was poured in to water (300 mL) and extracted with ethyl acetate (2×300 mL). The combined organic extracts were dried over anhydrous sodium sulphate, filtered, concentrated under vacuum to yield the crude product which was triturated with water (150 mL) to afford 4-chloro-3-cyano-N-[(3S,4R)-3-ethoxypiperidin-4-yl]-5-methyl-1H-pyrrole-2-carboxamide (670 mg, 55%) as solid.

Workup

  1. extractionextracted with ethyl acetate (2×300 mL)
  2. dry with materialThe combined organic extracts were dried over anhydrous sodium sulphate
  3. filtrationfiltered
  4. concentrationconcentrated under vacuum
  5. customto yield the crude product which
  6. customwas triturated with water (150 mL)

Sources & evidence

ORD record
ord-3302917e9ba04293833ead4aa176d621
Source dataset
uspto-grants-2011_12
Patent number
US08071605B2

Reaction notes

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