1,2-Dichloroethane → (S)-1-Methyl-pyrrolidine-2-carboxylic acid N'-(5-fluoro-3-methyl-pyridin-2-yl)-hydrazide

HRID 2282628Notes

Reaction equation

HRID 2282628 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH3:10])[C:5]([NH:8][NH2:9])=[N:6][CH:7]=1.[CH3:11][N:12]1[CH2:16][CH2:15][CH2:14][C@H:13]1[C:17](O)=[O:18].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([CH3:10])[C:5]([NH:8][NH:9][C:17]([C@@H:13]2[CH2:14][CH2:15][CH2:16][N:12]2[CH3:11])=[O:18])=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 643474N-Methyl-L-prolineHCID 534030065-Fluoro-2-hydrazinyl-3-methylpyridine

Product 1

HCID 86687172(S)-1-Methyl-pyrrolidine-2-carboxylic acid N'-(5-fluoro-3-methyl-pyridin-2-yl)-hydrazideYield 56.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of Intermediate 105b (76 mg, 0.537 mmol), (S)-1-methyl-pyrrolidine-2-carboxylic acid (55 mg, 0.72 mmol) and HOBT (8 mg, 0.72 mmol) in anhydrous DCM (5 mL) was treated with EDC (138 mg, 0.717 mmol) and stirred at RT under a nitrogen atmosphere for 18 h. The reaction mixture was diluted with DCM and washed with brine. The organic layer was dried (MgSO4) and concentrated in vacuo. The resultant residue was purified by FCC on silica, using a gradient of 1-10% MeOH in DCM, to afford the title compound (76 mg, 56%). 1H NMR (400 MHz, CDCl3): 1.74-2.05 (3H, m), 2.15-2.33 (4H, m), 2.34-2.46 (1H, m), 2.52 (3H, s), 3.02-3.12 (1H, m), 3.15-3.25 (1H, m), 6.70 (1H, s), 7.08-7.18 (1H, m), 7.90 (1H, d, J=2.8 Hz), 9.52 (1H, br s).

Workup

  1. washwashed with brine
  2. dry with materialThe organic layer was dried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. customThe resultant residue was purified by FCC on silica

Sources & evidence

ORD record
ord-52bbfca4d48a44f686ffc73b91efa70b
Source dataset
uspto-grants-2015_09
Patent number
US09139584B2

Reaction notes

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