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

HRID 655776Notes

Reaction equation

HRID 655776 reaction equation
[Cl:1][C:2]1[C:3]([C:22]#[N:23])=[C:4]([C:8]([NH:10][C@@H:11]2[CH2:16][CH2:15][N:14](C(OC)=O)[CH2:13][C@@H:12]2[CH3:21])=[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:22]#[N:23])=[C:4]([C:8]([NH:10][C@@H:11]2[CH2:16][CH2:15][NH:14][CH2:13][C@@H:12]2[CH3:21])=[O:9])[NH:5][C:6]=1[CH3:7]

Participants

6

Reactant 4

HCID 962WaterHCID 14797Potassium HydroxideHCID 24654Hydrazine hydrate (1:1)HCID 59402504HCID 59402504, compound2×

Product 1

HCID 594026054-chloro-3-cyano-5-methyl-N-[(3S,4R)-3-methylpiperidin-4-yl]-1H-pyrrole-2-carboxamideYield 63.7%

Reagents, catalysts & solvents 1

HCID 174Ethylene GlycolSolvent

Procedure

A solution of methyl (3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methylpiperidine-1-carboxylate (Intermediate 42, 3.3 g, 8.39 mmol), potassium hydroxide (3.3 g, 58.77 mmol), and hydrazine hydrate (2.97 mL, 58.77 mmol) in ethylene glycol (200 mL) was stirred for 48 h at 120° C. The reaction mixture was poured in to water (200 mL), then extracted with ethyl acetate (2×250 mL). The combined organic layers were dried over anhydrous sodium sulphate, filtered, concentrated under vacuum to yield the crude product, which was triturated with water (100 mL) to afford 4-chloro-3-cyano-5-methyl-N-[(3S,4R)-3-methylpiperidin-4-yl]-1H-pyrrole-2-carboxamide 1.5 g (63%) as solid.

Workup

  1. extractionextracted with ethyl acetate (2×250 mL)
  2. dry with materialThe combined organic layers were dried over anhydrous sodium sulphate
  3. filtrationfiltered
  4. concentrationconcentrated under vacuum
  5. customto yield the crude product, which
  6. customwas triturated with water (100 mL)

Sources & evidence

ORD record
ord-ffdbe338d7014270a61c1d6ccc7b1935
Source dataset
uspto-grants-2011_12
Patent number
US08071605B2

Reaction notes

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