4-Aminopyridine → 2-{4-[2-(3,5-Dimethyl-pyrazol-1-yl)-acetyl]-piperazin-1-yl}-N-pyridin-4-yl-benzamide

HRID 1810958Notes

Reaction equation

HRID 1810958 reaction equation
[CH3:1][C:2]1[CH:6]=[C:5]([CH3:7])[N:4]([CH2:8][C:9]([N:11]2[CH2:16][CH2:15][N:14]([C:17]3[CH:25]=[CH:24][CH:23]=[CH:22][C:18]=3[C:19](O)=[O:20])[CH2:13][CH2:12]2)=[O:10])[N:3]=1.C(Cl)(=O)C(Cl)=O.[NH2:32][C:33]1[CH:38]=[CH:37][N:36]=[CH:35][CH:34]=1.C(N(C(C)C)CC)(C)C>C(Cl)Cl.CN(C=O)C>[CH3:1][C:2]1[CH:6]=[C:5]([CH3:7])[N:4]([CH2:8][C:9]([N:11]2[CH2:12][CH2:13][N:14]([C:17]3[CH:25]=[CH:24][CH:23]=[CH:22][C:18]=3[C:19]([NH:32][C:33]3[CH:38]=[CH:37][N:36]=[CH:35][CH:34]=3)=[O:20])[CH2:15][CH2:16]2)=[O:10])[N:3]=1

Participants

7

Reactant 4

HCID 17274-AminopyridineHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 57516317{4-[2-(3,5-Dimethyl-pyrazol-1-yl)-acetyl]-piperazin-1-yl}-benzoic acid

Product 1

HCID 595488082-{4-[2-(3,5-Dimethyl-pyrazol-1-yl)-acetyl]-piperazin-1-yl}-N-pyridin-4-yl-benzamideYield 63%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

To 2-{4-[2-(3,5-dimethyl-pyrazol-1-yl)-acetyl]-piperazin-1-yl}-benzoic acid (0.051 g, 0.150 mmol) in 2 mL of CH2Cl2 at 4° C. is added 2 M oxalyl chloride solution (0.100 mL, 0.200 mmol) and 2 drops of dry DMF. The mixture is allowed to warm to room temperature over 1 h. To this is added 4-aminopyridine in one portion and diisopropylethyl amine (0.100 mL, 0.310 mmol). The mixture is stirred for 16 h. The mixture is concentrated and then purified via preparative HPLC (20-80% CH3CN/H2O). The product is further purified using a SiO2 prep-plate, eluting with (10% MeOH/CH2Cl2) to give 0.032 g of the title compound in 63% yield. MS MH+=419.2

Workup

  1. concentrationThe mixture is concentrated
  2. custompurified via preparative HPLC (20-80% CH3CN/H2O)
  3. customThe product is further purified
  4. washeluting with (10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-7d4bccab19574f75a4a8743ff6dfdf88
Source dataset
uspto-grants-2013_01
Patent number
US08362249B2

Reaction notes

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