1,1'-Carbonyldiimidazole → N-(1-Azabicyclo[3.3.1]non-5-ylmethyl)-5-chloro-2-methoxy-4-(methylamino)benzamide

HRID 5378

Reaction equation

HRID 5378 reaction equation
[Cl:1][C:2]1[C:3]([NH:13][CH3:14])=[CH:4][C:5]([O:11][CH3:12])=[C:6]([CH:10]=1)[C:7]([OH:9])=O.C(N1C=CN=C1)(N1C=CN=C1)=O.[N:27]12[CH2:35][C:31]([CH2:36][NH2:37])([CH2:32][CH2:33][CH2:34]1)[CH2:30][CH2:29][CH2:28]2>O1CCCC1.CO>[N:27]12[CH2:35][C:31]([CH2:36][NH:37][C:7](=[O:9])[C:6]3[CH:10]=[C:2]([Cl:1])[C:3]([NH:13][CH3:14])=[CH:4][C:5]=3[O:11][CH3:12])([CH2:32][CH2:33][CH2:34]1)[CH2:30][CH2:29][CH2:28]2

Participants

6

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 116942165-Chloro-2-methoxy-4-(methylamino)benzoic acidHCID 19795986{1-Azabicyclo[3.3.1]nonan-5-yl}methanamine

Product 1

HCID 19795975N-(1-Azabicyclo[3.3.1]non-5-ylmethyl)-5-chloro-2-methoxy-4-(methylamino)benzamideYield 73.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 5-chloro-2-methoxy-4-(methylamino)benzoic acid (1.08 g, 5 mmol) in anhydrous tetrahydrofuran (7 mL) under nitrogen was treated with 1,1'-carbonyldiimidazole (0.90 g, 5.5 mmol), stirred one hour, degassed under a stream of nitrogen for 10 minutes, and cooled (0° C.). A solution of 1-azabicyclo[3.3.1]nonane-5-methanamine (0.82 g, 5.3 mmol) in tetrahydrofuran (3 mL) was added dropwise, and stirring was continued at room temperature for 18 hours. The suspension was diluted with enough methanol to dissolve the solid, then the solution was filtered through a short column of alumina (eluted with 20% methanol/tetrahydrofuran). The filtrate was concentrated in vacuo, triturated from cold ether, and recrystallized from acetonitrile to afford 1.29 g (73%) of colorless crystals; mp 188°-190° C. (second phase), first phase melting point 175° C.

Workup

  1. customdegassed under a stream of nitrogen for 10 minutes
  2. stirringstirring
  3. waitwas continued at room temperature for 18 hours
  4. dissolutionto dissolve the solid
  5. filtrationthe solution was filtered through a short column of alumina (eluted with 20% methanol/tetrahydrofuran)
  6. concentrationThe filtrate was concentrated in vacuo
  7. customtriturated from cold ether
  8. customrecrystallized from acetonitrile

Sources & evidence

ORD record
ord-2a7ae11fb7f447428407b154948c0592
Source dataset
uspto-grants-1993_09
Patent number
US05244907

Linked notes

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