Pivaloyl chloride → Ethyl 5-(2-chloro-5-(6-pivalamidopyridin-2-yl)benzamido)-1-phenyl-1H-pyrazole-3-carboxylate

HRID 522112Notes

Reaction equation

HRID 522112 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:10]=[C:9]([NH:11][C:12](=[O:27])[C:13]2[CH:18]=[C:17]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([NH2:25])[N:20]=3)[CH:16]=[CH:15][C:14]=2[Cl:26])[N:8]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[N:7]=1)=[O:5])[CH3:2].[C:34](Cl)(=[O:39])[C:35]([CH3:38])([CH3:37])[CH3:36]>N1C=CC=CC=1>[Cl:26][C:14]1[CH:15]=[CH:16][C:17]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([NH:25][C:34](=[O:39])[C:35]([CH3:38])([CH3:37])[CH3:36])[N:20]=2)=[CH:18][C:13]=1[C:12]([NH:11][C:9]1[N:8]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[N:7]=[C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH:10]=1)=[O:27]

Participants

4

Reactant 2

HCID 62493Pivaloyl chlorideHCID 118456164Ethyl 5-(5-(6-aminopyridin-2-yl)-2-chlorobenzamido)-1-phenyl-1H-pyrazole-3-carboxylate

Product 1

HCID 118497045Ethyl 5-(2-chloro-5-(6-pivalamidopyridin-2-yl)benzamido)-1-phenyl-1H-pyrazole-3-carboxylateYield 92%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a solution of 5-(5-(6-aminopyridin-2-yl)-2-chlorobenzamido)-1-phenyl-1H-pyrazole-3-carboxylic acid ethyl ester (Preparation 2, 4.61 g, 10 mmol) in anhydrous pyridine (50 mL) was added pivaloyl chloride (1.32 g, 11 mmol) over 10 minutes with stirring at room temperature. The reaction was stirred for 90 minutes before concentrating in vacuo to low volume. The solution was partitioned between EtOAc (250 mL) and water (100 mL). The organic layer was separated, washed with brine (10 mL), dried over magnesium sulphate and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with 50% EtOAc in heptanes to afford the title compound (5 g, 92%).

Workup

  1. stirringThe reaction was stirred for 90 minutes
  2. concentrationbefore concentrating in vacuo to low volume
  3. customThe solution was partitioned between EtOAc (250 mL) and water (100 mL)
  4. customThe organic layer was separated
  5. washwashed with brine (10 mL)
  6. dry with materialdried over magnesium sulphate
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified
  9. washeluting with 50% EtOAc in heptanes

Sources & evidence

ORD record
ord-f999d98d38a142489f6ecf5765461cf1
Source dataset
uspto-grants-2016_05
Patent number
US09328096B2

Reaction notes

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