Dimethylformamide → 4-(Acetylamino)-5-chloro-N-(hexahydro-2,6-methano-1H-pyrrolizin-8-ylmethyl)-2-methoxybenzamide, hydrochloride

HRID 260715Notes

Reaction equation

HRID 260715 reaction equation
[C:1]([NH:4][C:5]1[C:13]([Cl:14])=[CH:12][C:8]([C:9]([OH:11])=O)=[C:7]([O:15][CH3:16])[CH:6]=1)(=[O:3])[CH3:2].C1N=CN([C:22]([N:24]2[CH:28]=N[CH:26]=[CH:25]2)=O)C=1.C[N:30]([CH:32]=O)C>>[ClH:14].[C:1]([NH:4][C:5]1[C:13]([Cl:14])=[CH:12][C:8]([C:9]([NH:30][CH2:32][CH:5]2[CH:13]3[CH2:28][N:24]4[CH2:22][CH:6]2[CH2:7][CH:25]4[CH2:26]3)=[O:11])=[C:7]([O:15][CH3:16])[CH:6]=1)(=[O:3])[CH3:2]

Participants

4

Reactant 3

HCID 6228Dimethylformamide2×HCID 682631,1'-CarbonyldiimidazoleHCID 109884964-Acetamido-5-chloro-2-methoxybenzoic acid

Product 1

HCID 1317194404-(Acetylamino)-5-chloro-N-(hexahydro-2,6-methano-1H-pyrrolizin-8-ylmethyl)-2-methoxybenzamide, hydrochlorideYield 54%

Procedure

4-Acetylamino-5-chloro-2-methoxybenzoic acid (235 mg, 0.965 mmol) and CDI (156 mg, 0.965 mmol) were dissolved in 5 ml of DMF and stirred for 0.5 hour. A solution of the amines of Example D (147 mg, 0.956 mmol) in 1 ml DMF was then added to the above solution. This mixture was stirred for 10 hours and concentrated to dryness. The residue was dissolved in CHCl3, washed successively with water and 10% K2CO3 and then dried over K2CO3, filtered and concentrated to dryness. The resulting solid was chromatographed with silica gel eluting with 15% MeOH (NH3)/CHCl3 to give a 51% (anti)/49%(syn) epimeric mixture of the title compound (196 mg, 54%). Conversion to the hydrochloride salt was accomplished by treatment with methanolic HCl.

Workup

  1. stirringThis mixture was stirred for 10 hours
  2. concentrationconcentrated to dryness
  3. dissolutionThe residue was dissolved in CHCl3
  4. washwashed successively with water and 10% K2CO3
  5. dry with materialdried over K2CO3
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customThe resulting solid was chromatographed with silica gel eluting with 15% MeOH (NH3)/CHCl3
  9. customto give a 51% (anti)/

Sources & evidence

ORD record
ord-57e56c77bc024348b8b11630577daa38
Source dataset
uspto-grants-1996_06
Patent number
US05530018

Reaction notes

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