Water → (S)-2-Methyl-piperidine-1-carboxylic acid N'-(5-fluoro-pyridin-2-yl)-hydrazide

HRID 630819Notes

Reaction equation

HRID 630819 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][NH2:9])=[N:6][CH:7]=1.CCN(C(C)C)C(C)C.[CH3:19][C@H:20]1[CH2:25][CH2:24][CH2:23][CH2:22][N:21]1[C:26](Cl)=[O:27].O>C(Cl)Cl.CO>[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][NH:9][C:26]([N:21]2[CH2:22][CH2:23][CH2:24][CH2:25][C@@H:20]2[CH3:19])=[O:27])=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 199167865-Fluoro-2-hydrazinylpyridineHCID 45081356(2S)-2-Methylpiperidine-1-carbonyl chloride

Product 1

HCID 86687104(S)-2-Methyl-piperidine-1-carboxylic acid N'-(5-fluoro-pyridin-2-yl)-hydrazideYield 57%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (5-fluoro-pyridin-2-yl)-hydrazine (582 mg, 4.58 mmol) and DIPEA (0.997 mL, 5.72 mmol) in dry DCM (20 mL) was added Intermediate 81a (740 mg, 4.58 mmol) and the resulting red solution stirred at RT for 66 h, and at reflux for 4 h. To the cooled solution was added water (20 mL) and the mixture shaken. The aqueous was extracted with DCM (20 mL), then the combined organics passed through a hydrophobic frit and concentrated in vacuo to leave a pale brown solid. FCC, using 0-5% MeOH in DCM, gave the title compound as a pale yellow solid (657 mg, 57%). 1H NMR (300 MHz, CDCl3): 1.22 (3H, d, J 6.9), 1.40-1.77 (6H, m), 2.96 (1H, td, J 13.0, 2.9), 3.85 (1H, ddd, J 13.3, 4.5, 2.2), 4.31 (1H, m), 6.50 (1H, s), 6.59 (1H, br s), 6.75 (1H, ddd, J 9.0, 3.6, 0.7), 7.27 (1H, ddd, J 9.1, 8.1, 3.1), 8.02 (1H, d, J 2.9).

Workup

  1. temperatureat reflux for 4 h
  2. stirringthe mixture shaken
  3. extractionThe aqueous was extracted with DCM (20 mL)
  4. concentrationconcentrated in vacuo
  5. customto leave a pale brown solid

Sources & evidence

ORD record
ord-4303def3c6c54618bf7018c6c48ec0df
Source dataset
uspto-grants-2016_04
Patent number
US09315503B2

Reaction notes

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