Ammonia → 3-(2-[(3-bromobenzyl)sulphanyl]-5-{[4-(1-pyrrolidinyl)-1-piperidinyl]carbonyl}-1H-benzimidazol-1-yl)-N-methyl-N-[2-(2-pyridinyl)ethyl]-1-propanamine

HRID 883694Notes

Reaction equation

HRID 883694 reaction equation
C(N1C=CN=C1)(N1C=CN=C1)=O.[Br:13][C:14]1[CH:15]=[C:16]([CH:44]=[CH:45][CH:46]=1)[CH2:17][S:18][C:19]1[N:23]([CH2:24][CH2:25][CH2:26][N:27]([CH3:36])[CH2:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][N:31]=2)[C:22]2[CH:37]=[CH:38][C:39]([C:41](O)=[O:42])=[CH:40][C:21]=2[N:20]=1.[N:47]1([CH:52]2[CH2:57][CH2:56][NH:55][CH2:54][CH2:53]2)[CH2:51][CH2:50][CH2:49][CH2:48]1.N.CN=C=S>C(Cl)(Cl)Cl.CN(C)C=O.O1CCCC1.ClCCl>[Br:13][C:14]1[CH:15]=[C:16]([CH:44]=[CH:45][CH:46]=1)[CH2:17][S:18][C:19]1[N:23]([CH2:24][CH2:25][CH2:26][N:27]([CH3:36])[CH2:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][N:31]=2)[C:22]2[CH:37]=[CH:38][C:39]([C:41]([N:55]3[CH2:56][CH2:57][CH:52]([N:47]4[CH2:51][CH2:50][CH2:49][CH2:48]4)[CH2:53][CH2:54]3)=[O:42])=[CH:40][C:21]=2[N:20]=1

Participants

10

Reactant 5

HCID 222AmmoniaHCID 11167Methyl isothiocyanateHCID 682631,1'-CarbonyldiimidazoleHCID 787034-(1-Pyrrolidinyl)piperidineHCID 690294842-[(3-bromobenzyl)thio]-1-{3-[methyl(2-pyridin-2-ylethyl)amino]propyl}-1H-benzimidazole-5-carboxylic acid

Product 1

HCID 575676493-(2-[(3-bromobenzyl)sulphanyl]-5-{[4-(1-pyrrolidinyl)-1-piperidinyl]carbonyl}-1H-benzimidazol-1-yl)-N-methyl-N-[2-(2-pyridinyl)ethyl]-1-propanamine

Reagents, catalysts & solvents 4

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
20 °C

Procedure

Carbonyldiimidazole (10.5 mg, 1.3 eq) in solution in chloroform (0.2 ml) is added to a solution of 2-[(3-bromobenzyl)thio]-1-{3-[methyl(2-pyridin-2-ylethyl)amino]propyl}-1H-benzimidazole-5-carboxylic acid (27 mg, 1 eq) in a mixture of dimethylformamide (0.2 ml) and tetrahydrofuran (0.4 ml). The mixture is stirred for 15 hours at approximately 20° C. then 4-(1-pyrrolidinyl)piperidine (15 mg, 2 eq) is added. After stirring for 15 hours at approximately 20° C., aminomethyl polystyrene resin (2 eq, acquired from Novabiochem), TBD-methyl polystyrene resin (2 eq, acquired from Novabiochem) and methylisothiocyanate polystyrene resin (4 eq, acquired from Novabiochem) are added to the mixture diluted in dichloromethane. After stirring for 6 hours at approximately 20° C., the mixture is filtered and the filtrate is concentrated under reduced pressure at 40° C. in order to produce the expected compound in the form of an oil (28 mg, 84% yield).

Workup

  1. stirringAfter stirring for 15 hours at approximately 20° C.
  2. stirringAfter stirring for 6 hours at approximately 20° C.
  3. filtrationthe mixture is filtered
  4. concentrationthe filtrate is concentrated under reduced pressure at 40° C. in order

Sources & evidence

ORD record
ord-adf292a3bd834466a5da188f79ce687b
Source dataset
uspto-grants-2012_08
Patent number
US08236965B2

Reaction notes

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