1,2-Dichloroethane → N-{[3-(6-{[(3S)-3-methyl-1-piperazinyl]methyl}-2-Pyridinyl)Phenyl]methyl}-3-(4-piperidinylmethyl)benzamide

HRID 2080334Notes

Reaction equation

HRID 2080334 reaction equation
CC(OC([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][C:15]2[CH:16]=[C:17]([CH:21]=[CH:22][CH:23]=2)[C:18]([OH:20])=O)[CH2:10][CH2:9]1)=O)(C)C.[NH2:24][CH2:25][C:26]1[CH:27]=[C:28]([C:32]2[N:37]=[C:36]([CH2:38][N:39]3[CH2:44][CH2:43][N:42](C(OC(C)(C)C)=O)[C@@H:41]([CH3:52])[CH2:40]3)[CH:35]=[CH:34][CH:33]=2)[CH:29]=[CH:30][CH:31]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C([O-])([O-])=O.[Na+].[Na+].C(O)(C(F)(F)F)=O>C(Cl)(Cl)Cl>[CH3:52][C@@H:41]1[NH:42][CH2:43][CH2:44][N:39]([CH2:38][C:36]2[N:37]=[C:32]([C:28]3[CH:27]=[C:26]([CH2:25][NH:24][C:18](=[O:20])[C:17]4[CH:21]=[CH:22][CH:23]=[C:15]([CH2:14][CH:11]5[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]5)[CH:16]=4)[CH:31]=[CH:30][CH:29]=3)[CH:33]=[CH:34][CH:35]=2)[CH2:40]1

Participants

8

Reactant 6

HCID 111,2-DichloroethaneHCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 757711-HydroxybenzotriazoleHCID 450739593-((1-(tert-Butoxycarbonyl)piperidin-4-yl)methyl)benzoic acidHCID 577366881,1-dimethylethyl (2S)-4-({6-[3-(aminomethyl)phenyl]-2-pyridinyl}methyl)-2-methyl-1-piperazinecarboxylate

Product 1

HCID 11707703N-{[3-(6-{[(3S)-3-methyl-1-piperazinyl]methyl}-2-Pyridinyl)Phenyl]methyl}-3-(4-piperidinylmethyl)benzamideYield 35.5%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a solution of the commercially available 3-[(1-{[(1,1-dimethylethyl)oxy]carbonyl}-4-piperidinyl)methyl]benzoic acid (40 mg, 0.13 mmol) in CHCl3 (2.0 mL) was added 1,1-dimethylethyl (2S)-4-({6-[3-(aminomethyl)phenyl]-2-pyridinyl}methyl)-2-methyl-1-piperazinecarboxylate (50 mg, 0.13 mmol), TEA (0.04 ml, 0.3 mmol), EDC (36 mg, 0.19 mmol) and HOBt (18 mg, 0.14 mmol). The reaction mixture was stirred at room temperature for 2 h, followed by addition of 0.5 mL of saturated Na2CO3. The organic layer was isolated via a hydrophobic frit followed by addition of 0.5 mL of TFA, and stirred at room temperature for 1 h. After removal of the solvent, the residue was purified by Gilson reverse phase HPLC, eluting with acetonitrile/water/0.1% TFA (10/90 to 70/30, v/v, over 12 in), to give the title compound (23 mg, 19%). LC/MS: m/z, 499 (M+H), 1.19 min.

Workup

  1. customThe organic layer was isolated via a hydrophobic frit
  2. stirringstirred at room temperature for 1 h
  3. customAfter removal of the solvent
  4. customthe residue was purified by Gilson reverse phase HPLC
  5. washeluting with acetonitrile/water/0.1% TFA (10/90 to 70/30, v/v, over 12 in)

Sources & evidence

ORD record
ord-966f4ff8aa58471da3b7f7c19cf67ba6
Source dataset
uspto-grants-2011_04
Patent number
US07932247B2

Reaction notes

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