1,2-Dichloroethane → 1-Dimethylamino-cyclopentanecarboxylic acid N'-(5-fluoro-pyridin-2-yl)-hydrazide

HRID 2282608Notes

Reaction equation

HRID 2282608 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][NH2:9])=[N:6][CH:7]=1.[CH3:10][N:11]([CH3:20])[C:12]1([C:17](O)=[O:18])[CH2:16][CH2:15][CH2:14][CH2:13]1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][NH:9][C:17]([C:12]2([N:11]([CH3:20])[CH3:10])[CH2:16][CH2:15][CH2:14][CH2:13]2)=[O:18])=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 199167865-Fluoro-2-hydrazinylpyridineHCID 220165611-(Dimethylamino)cyclopentane-1-carboxylic acid

Product 1

HCID 866871591-Dimethylamino-cyclopentanecarboxylic acid N'-(5-fluoro-pyridin-2-yl)-hydrazideYield 67%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (5-fluoro-pyridin-2-yl)-hydrazine (for reference procedure see WO 2010/022076, which is incorporated herein by reference in its entirety; 200 mg, 1.57 mmol) in DMF (10 mL) were added Intermediate 99a (247 mg, 1.57 mmol), EDC (333 mg, 1.73 mmol) and HOBt (21 mg, 0.16 mmol). The reaction mixture was stirred at RT for 18 h and then partitioned between EtOAc and water. The aqueous phase was further extracted with EtOAc (×3) and the combined organic layers were washed with brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was purified by FCC on silica, using a gradient of 0-8% (2M NH3 in MeOH) in DCM, to give the title compound (282 mg, 67%). 1H NMR (400 MHz, CDCl3): 1.54-1.73 (4H, m), 1.76-2.04 (4H, m), 2.25 (6H, s), 6.46 (1H, s), 6.64 (1H, dd, J=9.0, 3.5 Hz), 7.23-7.33 (1H, m), 8.04 (1H, d, J=3.0 Hz), 8.94 (1H, s).

Workup

  1. custompartitioned between EtOAc and water
  2. extractionThe aqueous phase was further extracted with EtOAc (×3)
  3. washthe combined organic layers were washed with brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe resultant residue was purified by FCC on silica

Sources & evidence

ORD record
ord-53e4fa1dc034472b95ec7485f2215843
Source dataset
uspto-grants-2015_09
Patent number
US09139584B2

Reaction notes

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