Dicyclohexylcarbodiimide → 4-Amino-N-(1-azabicyclo[2.2.2]octan-3-yl)-5-chloro-2-(cyclopropylmethoxy)benzene-1-carboximidic acid

HRID 2107941Notes

Reaction equation

HRID 2107941 reaction equation
[CH:1]1([CH2:4][O:5][C:6]2[CH:14]=[C:13]([NH2:15])[C:12]([Cl:16])=[CH:11][C:7]=2[C:8]([OH:10])=O)[CH2:3][CH2:2]1.Cl.Cl.[NH2:19][CH:20]1[CH:25]2[CH2:26][CH2:27][N:22]([CH2:23][CH2:24]2)[CH2:21]1.[OH-].[Na+].C1(N=C=NC2CCCCC2)CCCCC1>N1C=CC=CC=1.O>[N:22]12[CH2:27][CH2:26][CH:25]([CH2:24][CH2:23]1)[CH:20]([NH:19][C:8](=[O:10])[C:7]1[CH:11]=[C:12]([Cl:16])[C:13]([NH2:15])=[CH:14][C:6]=1[O:5][CH2:4][CH:1]1[CH2:2][CH2:3]1)[CH2:21]2

Participants

7

Reactant 4

HCID 10868Dicyclohexylcarbodiimide2×HCID 14798Sodium HydroxideHCID 197853Quinuclidine, 3-amino-, dihydrochlorideHCID 14403895HCID 14403895, compound

Product 1

HCID 713424-Amino-N-(1-azabicyclo[2.2.2]octan-3-yl)-5-chloro-2-(cyclopropylmethoxy)benzene-1-carboximidic acidYield 93.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1049PyridineSolvent

Procedure

To a solution of 2-cyclopropylmethoxy-4-amino-5-chlorobenzoic acid (3.2 g; 0.0134 moles) in pyridine (15 ml), a solution of 3-aminoquinuclidine dihydrochloride (2.5 g; 0.0125 moles) and sodium hydroxide (0.5 g; 0.0125 moles) in water (15 ml) was added. To the resulting solution, N,N'-dicyclohexyl-carbodiimide (3.1 g; 0.0146 moles) was added and the mixture stirred at room temperature for 20 hours. An additional amount of N,N'-dicyclohexyl-carbodiimide (3.1 g; 0.0146 moles) was added and the mixture stirred for a further 24 hours. The insoluble solid was filtered off, washed with water and the solvent removed in vacuo at a temperature between 30° and 45° C. The solid residue was taken up in water, made alkaline with sodium hydroxide and a solid precipitated which was filtered off and dried to give N-(1-azabicyclo[2.2.2]oct-3-yl)-2-cyclopropylmethoxy-4-amino-5-chlorobenzamide (4.1 g) M.p. 183°-185° C. after recrystallisation from acetonitrile.

Workup

  1. stirringthe mixture stirred for a further 24 hours
  2. filtrationThe insoluble solid was filtered off
  3. washwashed with water
  4. customthe solvent removed in vacuo at a temperature between 30° and 45° C
  5. customa solid precipitated which
  6. filtrationwas filtered off
  7. customdried

Sources & evidence

ORD record
ord-130f7055b84d4c2b96d8de6f89d8ab12
Source dataset
uspto-grants-1990_06
Patent number
US04937236

Reaction notes

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