Pyridine → HCID 12052640, compound

HRID 1264087Notes

Reaction equation

HRID 1264087 reaction equation
[O:1]=[C:2]1[CH2:6][CH2:5][CH2:4][N:3]1[CH2:7][CH2:8][O:9][C:10]1[CH:18]=[CH:17][C:13]([C:14]([OH:16])=O)=[CH:12][CH:11]=1.C(Cl)(=O)C(Cl)=O.[CH3:25][O:26][C:27]1[CH:28]=[C:29]([CH:39]=[CH:40][C:41]=1[CH2:42][N:43]1[CH2:47][CH2:46][CH2:45][CH2:44]1)[CH2:30][NH:31][C:32]1[C:33]([NH2:38])=[CH:34][CH:35]=[CH:36][CH:37]=1.N1C=CC=CC=1.NC1C=CC=CC=1>ClCCl.CN(C=O)C>[CH3:25][O:26][C:27]1[CH:28]=[C:29]([CH:39]=[CH:40][C:41]=1[CH2:42][N:43]1[CH2:47][CH2:46][CH2:45][CH2:44]1)[CH2:30][NH:31][C:32]1[C:33]([NH:38][C:14](=[O:16])[C:13]2[CH:12]=[CH:11][C:10]([O:9][CH2:8][CH2:7][N:3]3[CH2:4][CH2:5][CH2:6][C:2]3=[O:1])=[CH:18][CH:17]=2)=[CH:34][CH:35]=[CH:36][CH:37]=1

Participants

8

Reactant 5

HCID 1049PyridineHCID 6115AnilineHCID 65578Oxalyl chlorideHCID 64972354-[2-(2-oxopyrrolidin-1-yl)ethoxy]benzoic acidHCID 12052632HCID 12052632, compound

Product 1

HCID 12052640HCID 12052640, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a suspension of 4-[2-(2-oxopyrrolidin-1-yl)ethoxy]-benzoic acid (250 mg, 1.0 mmol) in dry dichloromethane (10 mL) was added oxalyl chloride (0.184 mL, 2.1 mmol, 2.1 eq.) then a catalytic amount of DMF. After 1 h, the solvent was removed under reduced pressure. The residue was suspended in dry dichloromethane (9 mL) then added portionwise to a ) solution of N1-[3-methoxy-4-[(1-pyrrolidinyl)methyl]benzyl]-1,2-benzenediamine (prepared according to Example 6, Part E) (292 mg, 0.94 mmol, 0.94 eq.) in dry dichloromethane (1 mL) and pyridine (0.182 mL, 2.25 mmol, 2.25 eq.) at 0° C. until all of the aniline had been consumed by tlc (9:1 CHCl3:MeOH). The reaction mixture was allowed to warm to ambient temperature then quenched with the addition of a saturated aqueous solution of sodium bicarbonate (10 mL). The reaction mixture was diluted with ethyl acetate (50 mL) then the layers were separated. The organic layer was dried (MgSO4), filtered, then concentrated under reduced pressure. The amide was obtained as a tan foam (140 mg, 26%) after flash chromatography (2-10% MeOH, 0.5% TEA in CHCl3).

Workup

  1. customthe solvent was removed under reduced pressure
  2. customhad been consumed by tlc (9:1 CHCl3:MeOH)
  3. customthen quenched with the addition of a saturated aqueous solution of sodium bicarbonate (10 mL)
  4. additionThe reaction mixture was diluted with ethyl acetate (50 mL)
  5. customthe layers were separated
  6. dry with materialThe organic layer was dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-daa68b28e5f24f4ba1fc60863d6db3ca
Source dataset
uspto-grants-2003_04
Patent number
US06541499B1

Reaction notes

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