2,2-Dimethylsuccinic anhydride → 4-(4-{5-[(4-Chloro-benzo[b]thiophene-2-carbonyl)-amino]-pyridin-2-yl}-piperazin-1-yl)-2,2-dimethyl-4-oxo-butyric acid

HRID 1645346

Reaction equation

HRID 1645346 reaction equation
[N:1]1([C:7]2[N:12]=[CH:11][C:10]([NH:13][C:14]([C:16]3[S:20][C:19]4[CH:21]=[CH:22][CH:23]=[C:24]([Cl:25])[C:18]=4[CH:17]=3)=[O:15])=[CH:9][CH:8]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[CH3:26][C:27]1([CH3:34])[CH2:32][C:31](=[O:33])[O:30][C:28]1=[O:29]>C(Cl)Cl>[Cl:25][C:24]1[C:18]2[CH:17]=[C:16]([C:14]([NH:13][C:10]3[CH:9]=[CH:8][C:7]([N:1]4[CH2:6][CH2:5][N:4]([C:31](=[O:33])[CH2:32][C:27]([CH3:34])([CH3:26])[C:28]([OH:30])=[O:29])[CH2:3][CH2:2]4)=[N:12][CH:11]=3)=[O:15])[S:20][C:19]=2[CH:21]=[CH:22][CH:23]=1

Participants

4

Reactant 2

HCID 870672,2-Dimethylsuccinic anhydrideHCID 593651784-Chloro-benzo[b]thiophene-2-carboxylic acid (6-piperazin-1-yl-pyridin-3-yl)-amide

Product 1

HCID 462078284-(4-{5-[(4-Chloro-benzo[b]thiophene-2-carbonyl)-amino]-pyridin-2-yl}-piperazin-1-yl)-2,2-dimethyl-4-oxo-butyric acidYield 89.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 4-chloro-benzo[b]thiophene-2-carboxylic acid (6-piperazin-1-yl-pyridin-3-yl)-amide (50 mg, 0.13 mmol), CH2Cl2 (5 mL), and TEA (40 mg, 0.39 mmol) was stirred at room temperature. 2,2-Dimethylsuccinic anhydride (36 mg, 0.28 mmol) was added slowly. The reaction was stirred at room temperature for 0.5 hr then concentrated and the residue was taken up into 50 mL of EtOAc and washed with 50 mL of saturated ammonium chloride, brine and dried over anhydrous sodium sulfate. The solvent was removed and the product was triturated with diethyl ether and hexanes followed by filtration, to afford the product 4-(4-{5-[(4-chloro-benzo[b]thiophene-2-carbonyl)-amino]-pyridin-2-yl}-piperazin-1-yl)-2,2-dimethyl-4-oxo-butyric acid (58 mg, 89% yield). LCMS for C24H25ClN4O4S calcd. (m/e) 500, observed 499 (M−H).

Workup

  1. stirringThe reaction was stirred at room temperature for 0.5 hr
  2. concentrationthen concentrated
  3. washwashed with 50 mL of saturated ammonium chloride, brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was removed
  6. customthe product was triturated with diethyl ether and hexanes
  7. filtrationfollowed by filtration

Sources & evidence

ORD record
ord-851927c92ab04157a1b7523151f01bd0
Source dataset
uspto-grants-2012_02
Patent number
US08124766B2

Linked notes

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