Hydrochloric Acid → 1-(3-aminopropyl)-6-(piperidin-1-ylcarbonyl)-N-(3,4,5-trimethoxyphenyl)-1H-benzimidazol-2-amine dihydrochloride

HRID 1161001Notes

Reaction equation

HRID 1161001 reaction equation
C(N1C=CN=C1)(N1C=CN=C1)=O.C(OC([NH:20][CH2:21][CH2:22][CH2:23][N:24]1[C:28]2[CH:29]=[C:30]([C:33](O)=[O:34])[CH:31]=[CH:32][C:27]=2[N:26]=[C:25]1[NH:36][C:37]1[CH:42]=[C:41]([O:43][CH3:44])[C:40]([O:45][CH3:46])=[C:39]([O:47][CH3:48])[CH:38]=1)=O)(C)(C)C.[NH:49]1[CH2:54][CH2:53][CH2:52][CH2:51][CH2:50]1.[ClH:55]>C(Cl)(Cl)Cl.O1CCCC1.CN(C)C=O.ClCCl.C(OCC)(=O)C>[ClH:55].[ClH:55].[NH2:20][CH2:21][CH2:22][CH2:23][N:24]1[C:28]2[CH:29]=[C:30]([C:33]([N:49]3[CH2:54][CH2:53][CH2:52][CH2:51][CH2:50]3)=[O:34])[CH:31]=[CH:32][C:27]=2[N:26]=[C:25]1[NH:36][C:37]1[CH:42]=[C:41]([O:43][CH3:44])[C:40]([O:45][CH3:46])=[C:39]([O:47][CH3:48])[CH:38]=1

Participants

10

Reactant 4

HCID 313Hydrochloric AcidHCID 8082PiperidineHCID 682631,1'-CarbonyldiimidazoleHCID 687922531-{3-[(tert-butoxycarbonyl)amino]propyl}-2-[(3,4,5-trimethoxyphenyl)amino]-1H-benzimidazole-6-carboxylic acid

Product 1

HCID 117570511-(3-aminopropyl)-6-(piperidin-1-ylcarbonyl)-N-(3,4,5-trimethoxyphenyl)-1H-benzimidazol-2-amine dihydrochlorideYield 65%

Reagents, catalysts & solvents 5

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
20 °C

Procedure

A solution of carbonyldiimidazole (CDI) (18 mg, 1.1 eq) in chloroform (0.2 ml) is added to a solution of 1-{3-[(tert-butoxycarbonyl)amino]propyl}-2-[(3,4,5-trimethoxyphenyl)amino]-1H-benzimidazole-6-carboxylic acid (50 mg, 1 eq) in tetrahydrofuran (0.45 ml) and dimethylformamide (0.05 ml). The mixture is stirred for 16 hours at a temperature of approximately 20° C., then a solution of piperidine (17 mg, 2 eq) in tetrahydrofuran (0.2 ml) is added. After stirring for 18 hours at a temperature of approximately 20° C., the mixture is diluted with dichloromethane (3 ml), and aminomethylpolystyrene resin (2 eq), TBD-methyl-polystyrene resin (2 eq) and methylisothiocyanate-polystyrene resin (4 eq) are added. After stirring for 6 hours at approximately 20° C., the mixture is filtered and the filtrate is concentrated under reduced pressure at 40° C. The residue obtained is dissolved in ethyl acetate (0.5 ml) and a solution of hydrochloric acid (1N in diethyl ether, 3 ml) is added. After stirring for 1 hour at a temperature of approximately 20° C., the precipitate obtained is filtered and dried in order to produce the expected compound (35 mg, 65%).

Workup

  1. stirringAfter stirring for 18 hours at a temperature of approximately 20° C.
  2. additionare added
  3. stirringAfter stirring for 6 hours at approximately 20° C.
  4. filtrationthe mixture is filtered
  5. concentrationthe filtrate is concentrated under reduced pressure at 40° C
  6. customThe residue obtained
  7. stirringAfter stirring for 1 hour at a temperature of approximately 20° C.
  8. customthe precipitate obtained
  9. filtrationis filtered
  10. customdried in order

Sources & evidence

ORD record
ord-e5a1202858304e0e80ad86e2ea6baede
Source dataset
uspto-grants-2010_10
Patent number
US07816539B2

Reaction notes

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