HCID 701019, compound → HCID 86664325, compound

HRID 1753887Notes

Reaction equation

HRID 1753887 reaction equation
Cl[C:2]1[C:7]([C:8]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)=[O:9])=[C:6]([CH3:19])[CH:5]=[C:4]([Cl:20])[N:3]=1.[CH:21]([Mg]Cl)([CH3:23])[CH3:22]>C1COCC1>[Cl:20][C:4]1[N:3]=[C:2]([CH:21]([CH3:23])[CH3:22])[C:7]([C:8]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)=[O:9])=[C:6]([CH3:19])[CH:5]=1

Participants

4

Reactant 2

HCID 701019HCID 701019, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 86664325HCID 86664325, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
10 °C

Procedure

A solution of 6.0 g (18.3 mmol) 2,6-dichloro-N-(4-chlorobenzyl)-4-methyl-pyridine-3-carboxylic acid amide (synthesized according to the method described in section a) of example 2) in THF (180 ml) and NMP (60 ml) was degassed for 30 min followed by the addition of 1.3 g (3.7 mmol) Fe(acac)3. This mixture was degassed again for 20 min. At −40° C. 137 ml (2M in THF, 274 mmol) isopropylmagnesiumchloride was added dropwise over 1 h. The reaction mixture was allowed to reach 0° C. and was quenched at this temperature with a sat. aq. NH4Cl sol. followed by stirring at 10° C. for 30 min. Then the mixture was diluted with EtOAc and the organic layer was separated, washed with water and brine, dried over Na2SO4 and concentrated in vacuo. Purification of the residue by CC (hexane/EtOAc 9:1) provided 2.45 g (7.3 mmol, 40%) 6-chloro-N-(4-chlorobenzyl)-2-isopropyl-4-methyl-pyridine-3-carboxylic amide.

Workup

  1. customNMP (60 ml) was degassed for 30 min
  2. customThis mixture was degassed again for 20 min
  3. customAt −40° C
  4. customto reach 0° C.
  5. customwas quenched at this temperature with a sat. aq. NH4Cl sol.
  6. additionThen the mixture was diluted with EtOAc
  7. customthe organic layer was separated
  8. washwashed with water and brine
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated in vacuo
  11. customPurification of the residue by CC (hexane/EtOAc 9:1)

Sources & evidence

ORD record
ord-6fbb11c54a894de581509e9442ae45d8
Source dataset
uspto-grants-2015_10
Patent number
US09168259B2

Reaction notes

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