1,2-Dichloroethane → HCID 86687066, compound

HRID 630782Notes

Reaction equation

HRID 630782 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][NH2:9])=[N:6][CH:7]=1.Cl.[CH3:11][N:12]1[CH2:19][CH2:18][CH2:17][C@@H:13]1[C:14](O)=[O:15].C1C=CC2N(O)N=NC=2C=1.O.C(Cl)CCl>C(Cl)Cl.C([O-])(O)=O.[Na+].[Na+].[Cl-]>[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][NH:9][C:14]([C@H:13]2[CH2:17][CH2:18][CH2:19][N:12]2[CH3:11])=[O:15])=[N:6][CH:7]=1

Participants

9

Reactant 5

HCID 111,2-DichloroethaneHCID 962WaterHCID 757711-HydroxybenzotriazoleHCID 199167865-Fluoro-2-hydrazinylpyridineHCID 53393776HCID 53393776, compound

Product 1

HCID 86687066HCID 86687066, compoundYield 65.4%

Reagents, catalysts & solvents 3

HCID 5234Sodium ChlorideSolventHCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A mixture of (5-fluoro-pyridin-2-yl)-hydrazine (889 mg, 7.00 mmol), N-methyl-D-proline hydrochloride (1.274 g, 7.7 mmol) and HOBt.H2O (95 mg, 0.70 mmol) in DCM (20 mL) was treated with EDC (1.494 g, 7.8 mmol), and the mixture stirred at RT for 6.5 h. The mixture was then diluted with sat. aq. NaHCO3 solution, NaCl added, and the mixture extracted with DCM (8×20 mL). The combined organics were dried and concentrated in vacuo to give (R)-1-methyl-pyrrolidine-2-carboxylic acid N′-(5-fluoro-pyridin-2-yl)-hydrazide as a pale orange solid (1.09 g). This was dissolved in THF (20 mL) then Ph3P (2.40 g, 9.16 mmol), Et3N (2.6 mL, 18.3 mmol), and hexachloroethane (2.17 g, 9.16 mmol) added sequentially. The mixture was stirred at RT for 4 h, then was filtered, the filter-cake washed with diethyl ether, and the combined organics concentrated in vacuo. The residue was purified on a SCX-2 cartridge (50 g), washing with methanol then eluting basic components with 0.2-2 M ammonia in methanol. Product containing fractions were combined and concentrated in vacuo. The residue was further purified by FCC, using 0-100% EtOAc in cyclohexane, then 8-10% MeOH in EtOAc, to give the title compound as a pale red oil (876 mg, 57%). LCMS (Method 3): Rt 0.55 min, m/z 221 [MH+].

Workup

  1. additionadded
  2. extractionthe mixture extracted with DCM (8×20 mL)
  3. customThe combined organics were dried
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7d22b1c2c1e44923abf135432af71302
Source dataset
uspto-grants-2016_04
Patent number
US09315503B2

Reaction notes

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