Sodium Carbonate → cis-4-amino-N-[1-[3-(2-benzothiazolylamino)propyl]-3-methoxy-4-piperidinyl]-5-chloro-2-methoxybenzamide

HRID 654184Notes

Reaction equation

HRID 654184 reaction equation
Cl[C:2]1[S:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.[NH2:11][C:12]1[C:32]([Cl:33])=[CH:31][C:15]([C:16]([NH:18][C@H:19]2[CH2:24][CH2:23][N:22]([CH2:25][CH2:26][CH2:27][NH2:28])[CH2:21][C@H:20]2[O:29][CH3:30])=[O:17])=[C:14]([O:34][CH3:35])[CH:13]=1.C(=O)([O-])[O-].[Na+].[Na+]>CC1C=CC=CC=1>[NH2:11][C:12]1[C:32]([Cl:33])=[CH:31][C:15]([C:16]([NH:18][C@H:19]2[CH2:24][CH2:23][N:22]([CH2:25][CH2:26][CH2:27][NH:28][C:2]3[S:3][C:4]4[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=4[N:6]=3)[CH2:21][C@H:20]2[O:29][CH3:30])=[O:17])=[C:14]([O:34][CH3:35])[CH:13]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 119872-ChlorobenzothiazoleHCID 14854959HCID 14854959, compound

Product 1

HCID 14855070cis-4-amino-N-[1-[3-(2-benzothiazolylamino)propyl]-3-methoxy-4-piperidinyl]-5-chloro-2-methoxybenzamideYield 41.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 1.9 parts of 2-chlorobenzothiazole, 3.7 parts of cis-4-amino-N-[1-(3-aminopropyl)-3-methoxy-4-piperidinyl]-5-chloro-2-methoxybenzamide and 22.5 parts of methylbenzene was stirred and refluxed overnight. 1.6 Parts of sodium carbonate were added and the whole was stirred for 4 hours at reflux temperature. The methylbenzene layer was washed with water and set aside. The precipitated product, which was formed during the reaction, was filtered off and dissolved in trichloromethane. The solution was washed with water. The combined organic layers (trichloromethane and methylbenzene layers) were dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol, saturated with ammonia, (95:5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from acetonitrile. The product was filtered off and dried, yielding 2.06 parts (41.2%) of cis-4-amino-N-[1-[3-(2-benzothiazolylamino)propyl]-3-methoxy-4-piperidinyl]-5-chloro-2-methoxybenzamide; mp. 161.5° C. (compound 45).

Workup

  1. temperaturerefluxed overnight
  2. stirringthe whole was stirred for 4 hours
  3. temperatureat reflux temperature
  4. washThe methylbenzene layer was washed with water
  5. customThe precipitated product, which was formed during the reaction
  6. filtrationwas filtered off
  7. dissolutiondissolved in trichloromethane
  8. washThe solution was washed with water
  9. dry with materialThe combined organic layers (trichloromethane and methylbenzene layers) were dried
  10. filtrationfiltered
  11. customevaporated
  12. customThe residue was purified by column chromatography over silica gel using
  13. additiona mixture of trichloromethane and methanol
  14. customThe pure fractions were collected
  15. customthe eluent was evaporated
  16. customThe residue was crystallized from acetonitrile
  17. filtrationThe product was filtered off
  18. customdried

Sources & evidence

ORD record
ord-093e5bf12a9646e8996638f904c63ac9
Source dataset
uspto-grants-1992_07
Patent number
US05130312

Reaction notes

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