Ammonium Hydroxide → 4-Amino-5-chloro-2-methoxy-N-(tetrahydro-1H-pyrrolizin-7a(5H)-ylethyl)benzamide

HRID 976442Notes

Reaction equation

HRID 976442 reaction equation
[NH2:1][C:2]1[C:10]([Cl:11])=[CH:9][C:5]([C:6]([OH:8])=O)=[C:4]([O:12][CH3:13])[CH:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[CH2:26]1[C:33]2([CH2:34][CH2:35][NH2:36])[N:29]([CH2:30][CH2:31][CH2:32]2)[CH2:28][CH2:27]1.[NH4+].[OH-]>CO.C(Cl)(Cl)Cl.CN(C=O)C>[NH2:1][C:2]1[C:10]([Cl:11])=[CH:9][C:5]([C:6]([NH:36][CH2:35][CH2:34][C:33]23[CH2:26][CH2:27][CH2:28][N:29]2[CH2:30][CH2:31][CH2:32]3)=[O:8])=[C:4]([O:12][CH3:13])[CH:3]=1

Participants

7

Reactant 4

HCID 14923Ammonium HydroxideHCID 682631,1'-CarbonyldiimidazoleHCID 816264-Amino-5-chloro-2-methoxybenzoic acidHCID 107969772-(Hexahydro-1H-pyrrolizin-7a-yl)ethanamine

Product 1

HCID 152249414-Amino-5-chloro-2-methoxy-N-(tetrahydro-1H-pyrrolizin-7a(5H)-ylethyl)benzamideYield 75.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21584188Chloroform methanolSolvent

Procedure

4-Amino-5-chloro-2-methoxybenzoic acid (1.0 g, 0.005 moles) and 1,1'-carbonyldi-imidazole (892 mg, 0.00055 moles) were suspended in the DMF (10 ml) and the mixture was stirred until solution occurred (three hours). At this time, tetrahydro-1H-pyrrolizin-7a(5H)-ethylamine [amine Heterocycles 16, 755, 1981](771 mg; 0,005 moles) was added and the mixture was stirred for 1 hour. Tlc 30% MeOH/CHCl3 /1/10% NH4OH indicated that the reaction was complete. Concentration afforded a residue which was partitioned between Et2O/H2O . The product crystallized. The solid was filtered and dissolved in CHCl3, washed with dilute K2CO3, dried over MgSO4 and concentrated to a solid. The solid was triturated with Et2O and converted to the HCl salt with MeOH/HCl to yield 1.27g (69%) of the product.

Workup

  1. custom(three hours)
  2. stirringthe mixture was stirred for 1 hour
  3. concentrationConcentration
  4. customafforded a residue which
  5. customwas partitioned between Et2O/H2O
  6. customThe product crystallized
  7. filtrationThe solid was filtered
  8. dissolutiondissolved in CHCl3
  9. washwashed with dilute K2CO3
  10. dry with materialdried over MgSO4
  11. concentrationconcentrated to a solid
  12. customThe solid was triturated with Et2O

Sources & evidence

ORD record
ord-290e5d61aaf64244ae58a6b2d3d80367
Source dataset
uspto-grants-1997_03
Patent number
US05612366

Reaction notes

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