1,2-Dichloroethane → N-{[3-(5-{[(3S)-3-methyl-1-piperazinyl]methyl}-2-thienyl)phenyl]methyl}-3-(4-piperidinylmethyl)benzamide

HRID 2080333Notes

Reaction equation

HRID 2080333 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[S:36][C:35]([CH2:37][N:38]3[CH2:43][CH2:42][N:41](C(OC(C)(C)C)=O)[C@@H:40]([CH3:51])[CH2:39]3)=[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(Cl)(Cl)Cl>[CH3:51][C@@H:40]1[NH:41][CH2:42][CH2:43][N:38]([CH2:37][C:35]2[S:36][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]=2)[CH2:39]1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 10340Sodium CarbonateHCID 757711-HydroxybenzotriazoleHCID 450739593-((1-(tert-Butoxycarbonyl)piperidin-4-yl)methyl)benzoic acidHCID 577367081,1-dimethylethyl (2S)-4-({5-[3-(aminomethyl)phenyl]-2-thienyl)methyl)-2-methyl-1-piperazinecarboxylate

Product 1

HCID 11549650N-{[3-(5-{[(3S)-3-methyl-1-piperazinyl]methyl}-2-thienyl)phenyl]methyl}-3-(4-piperidinylmethyl)benzamideYield 52%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a solution of 3-[(1-{[(1,1-dimethylethyl)oxy]carbonyl}-4-piperidinyl)methyl]benzoic acid (319 mg, 1.0 mmol) in CHCl3 (5.0 mL) was added 1,1-dimethylethyl (2S)-4-({5-[3-(aminomethyl)phenyl]-2-thienyl)methyl)-2-methyl-1-piperazinecarboxylate (401 mg, 1.0 mmol), TEA (0.26 ml, 2 mmol), EDC (288 mg, 1.5 mmol) and HOBt (150 mg, 1.1 mmol). The reaction mixture was stirred at room temperature for 2 h, followed by addition of 1 mL of saturated Na2CO3. The organic layer was dried over Na2SO4, and filtered. The filtrate was mixed with 1 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 min), to give the title compound (261 mg, 52%). LC/MS: m/z, 502 (M+H), 1.31 min.

Workup

  1. dry with materialThe organic layer was dried over Na2SO4
  2. filtrationfiltered
  3. additionThe filtrate was mixed with 1 mL of TFA
  4. stirringstirred at room temperature for 1 h
  5. customAfter removal of the solvent
  6. customthe residue was purified by Gilson reverse phase HPLC
  7. washeluting with acetonitrile/water/0.1% TFA (10/90 to 70/30, v/v, over 12 min)

Sources & evidence

ORD record
ord-4887f55134df4eeb80f1fe33e7c264fb
Source dataset
uspto-grants-2011_04
Patent number
US07932247B2

Reaction notes

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