Oxalyl chloride → HCID 59548757, compound

HRID 1810971Notes

Reaction equation

HRID 1810971 reaction equation
[CH3:1][S:2]([C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=O)=[CH:7][CH:6]=1)(=[O:4])=[O:3].C(Cl)(=O)C(Cl)=O.[NH2:20][C:21]1[C:22]([N:28]2[CH2:33][CH2:32][N:31]([C:34](=[O:43])[CH2:35][N:36]3[C:40]([CH3:41])=[CH:39][C:38]([CH3:42])=[N:37]3)[CH2:30][CH2:29]2)=[N:23][CH:24]=[C:25]([Cl:27])[CH:26]=1.C(N(CC)C(C)C)(C)C>C(Cl)Cl.CN(C)C=O>[Cl:27][C:25]1[CH:26]=[C:21]([NH:20][C:9](=[O:11])[C:8]2[CH:7]=[CH:6][C:5]([S:2]([CH3:1])(=[O:3])=[O:4])=[CH:13][CH:12]=2)[C:22]([N:28]2[CH2:33][CH2:32][N:31]([C:34](=[O:43])[CH2:35][N:36]3[C:40]([CH3:41])=[CH:39][C:38]([CH3:42])=[N:37]3)[CH2:30][CH2:29]2)=[N:23][CH:24]=1

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 77670p-(Methylsulphonyl)benzoic acidHCID 81531DiisopropylethylamineHCID 59548857HCID 59548857, compound

Product 1

HCID 59548757HCID 59548757, compoundYield 36%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-methanesulfonyl-benzoic acid (0.030 g, (0.150 mmol) in methylene chloride (2 mL) is added oxalyl chloride (0.017 mL, 0.200 mmol) followed by 1 drop of N,N-dimethylformamide. Vigourous bubbling is observed and the reaction mixture is stirred at room temperature for 2 h. The mixture is concentrated under a stream of nitrogen. The residue is dissolved in methylene chloride (2 mL) and 1-[4-(3-amino-5-chloro-pyridin-2-yl)-piperazin-1-yl]-2-(3,5-dimethyl-pyrazol-1-yl)-ethanone (0.040 g, 0.110 mmol) is added followed by (0.040 mL, 0.220 mmol) N,N-diisopropylethylamine (0.040 mL, 0.220 mmol). The mixture is stirred at room temperature for 3 days then concentrated under a stream of nitrogen. The residue is dissolved in dimethylsulfoxide and purified by reverse phase preparative HPLC to provide, after removal of the eluent, 0.022 g of N-(5-Chloro-2-{4-[2-(3,5-dimethyl-pyrazol-1-yl)-acetyl]-piperazin-1-yl}-pyridin-3-yl)-4-methanesulfonyl-benzamide as a white solid in 36% yield. MS; MH+=531.8

Workup

  1. customVigourous bubbling
  2. concentrationThe mixture is concentrated under a stream of nitrogen
  3. dissolutionThe residue is dissolved in methylene chloride (2 mL)
  4. stirringThe mixture is stirred at room temperature for 3 days
  5. concentrationthen concentrated under a stream of nitrogen
  6. dissolutionThe residue is dissolved in dimethylsulfoxide
  7. custompurified by reverse phase preparative HPLC
  8. customto provide
  9. customafter removal of the eluent, 0.022 g of N-(5-Chloro-2-{4-[2-(3,5-dimethyl-pyrazol-1-yl)-acetyl]-piperazin-1-yl}-pyridin-3-yl)-4-methanesulfonyl-benzamide as a white solid in 36% yield

Sources & evidence

ORD record
ord-6bc0d900911f4b89bf0425e2a7de0671
Source dataset
uspto-grants-2013_01
Patent number
US08362249B2

Reaction notes

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