Acetic Acid → 3-{5-amino-4-[3-(4-methyl-piperazin-1-ylmethyl)-benzoyl]-pyrazol-1-yl}-N-cyclopropyl-4-methyl-benzamide

HRID 1959495Notes

Reaction equation

HRID 1959495 reaction equation
[NH2:1][C:2]1[N:6]([C:7]2[CH:8]=[C:9]([CH:16]=[CH:17][C:18]=2[CH3:19])[C:10]([NH:12][CH:13]2[CH2:15][CH2:14]2)=[O:11])[N:5]=[CH:4][C:3]=1[C:20](=[O:29])[C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([CH:27]=O)[CH:22]=1.[CH3:30][N:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1.CC(O)=O.[OH-].[Na+]>ClCCl.ClCCCl>[NH2:1][C:2]1[N:6]([C:7]2[CH:8]=[C:9]([CH:16]=[CH:17][C:18]=2[CH3:19])[C:10]([NH:12][CH:13]2[CH2:14][CH2:15]2)=[O:11])[N:5]=[CH:4][C:3]=1[C:20](=[O:29])[C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([CH2:27][N:34]2[CH2:35][CH2:36][N:31]([CH3:30])[CH2:32][CH2:33]2)[CH:22]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 531671-MethylpiperazineHCID 112806793-[5-amino-4-(3-formylbenzoyl)-pyrazol-1-yl]-N-cyclopropyl-4-methylbenzamide

Product 1

HCID 117518073-{5-amino-4-[3-(4-methyl-piperazin-1-ylmethyl)-benzoyl]-pyrazol-1-yl}-N-cyclopropyl-4-methyl-benzamideYield 67%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

To a mixture of 3-[5-amino-4-(3-formyl-benzoyl)-pyrazol-1-yl]-N-cyclopropyl-4-methyl-benzamide 6 (Example 9, 1.0 eq) and 1-methyl-piperazine (1.09 eq) in equal volume of 1,2-dichloroethane and dichloromethane was added AcOH (0.96 eq) Sodium triacetoxyborohydride (1.5 eq) was then added. The reaction mixture was stirred at room temperature for 2 h. Aqueous NaOH was added to quench the reaction and the mixture was extracted with ethyl acetate. The organic layer was separated and washed with water and saturated NaCl solution. The organic layer was then dried over Na2SO4, filtered and concentrated to give a residue that could be purified by silica gel chromatography (eluent: 9/1 CH2Cl2/methanol then 9/1/0.05 CH2Cl2/MeOH/NH3H2O). Yield 67%. MS m/z 473.3 [M+H]+; 1H NMR (300 MHz, CDCl3) δ0.61 (m, 2H), 0.86 (m, 2H), 2.26 (s, 3H), 2.30 (s, 3H), 2.52 (brs, 8H), 2.90 (m, 1H), 3.60 (s, 2H), 5.87 (brs, 1H), 6.30 (brs, 2H), 7.45 (m, 3H), 7.70 (m, 2H), 7.83 (m, 3H) ppm.

Workup

  1. additionwas then added
  2. customto quench
  3. customthe reaction
  4. extractionthe mixture was extracted with ethyl acetate
  5. customThe organic layer was separated
  6. washwashed with water and saturated NaCl solution
  7. dry with materialThe organic layer was then dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give a residue that
  11. customcould be purified by silica gel chromatography (eluent

Sources & evidence

ORD record
ord-cdb1669a81f44858ac027f1e3a16b91a
Source dataset
uspto-grants-2013_04
Patent number
US08410160B2

Reaction notes

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