Benzenesulfonyl chloride → [1-(4-Benzenesulfonylamino-benzyl)-3,5-dimethyl-1H-pyrazol-4-yl]-acetic acid

HRID 1631912Notes

Reaction equation

HRID 1631912 reaction equation
C[O:2][C:3](=[O:20])[CH2:4][C:5]1[C:6]([CH3:19])=[N:7][N:8]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([NH2:18])=[CH:14][CH:13]=2)[C:9]=1[CH3:10].C(N(CC)CC)C.[C:28]1([S:34](Cl)(=[O:36])=[O:35])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>ClCCl>[C:28]1([S:34]([NH:18][C:15]2[CH:16]=[CH:17][C:12]([CH2:11][N:8]3[C:9]([CH3:10])=[C:5]([CH2:4][C:3]([OH:2])=[O:20])[C:6]([CH3:19])=[N:7]3)=[CH:13][CH:14]=2)(=[O:36])=[O:35])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

5

Reactant 3

HCID 7369Benzenesulfonyl chlorideHCID 8471TriethylamineHCID 66707335[1-(4-aminobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl]acetic acid methyl ester2×

Product 1

HCID 58071742[1-(4-Benzenesulfonylamino-benzyl)-3,5-dimethyl-1H-pyrazol-4-yl]-acetic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Sulfonamide formation: To a solution of [1-(4-amino-benzyl)-3,5-dimethyl-1H-pyrazol-4-yl]-acetic acid methyl ester (intermediate 1.1.3, 54 mg, 0.20 mmol) in dichloromethane (1 mL) was added triethylamine (72 μL, 0.51 mmol) and phenylsulfonyl chloride (36 μL, 0.25 mmol). The reaction mixture was stirred for 1 h at room temperature. The reaction mixture was filtered over Alox B, eluting with 10% methanol in dichloromethane. Saponification: After removing the volatiles under reduced pressure, the remaining residue was dissolved in methanol (0.5 mL) and treated with aqueous LiOH solution (1 M, 0.4 mL). After 1.5 h, the mixture was neutralized and purified via preparative reversed phase HPLC (gradient of methanol in water+0.1% trifluoroacetic acid).

Workup

  1. filtrationThe reaction mixture was filtered over Alox B
  2. washeluting with 10% methanol in dichloromethane
  3. customSaponification: After removing the volatiles under reduced pressure
  4. dissolutionthe remaining residue was dissolved in methanol (0.5 mL)
  5. additiontreated with aqueous LiOH solution (1 M, 0.4 mL)
  6. waitAfter 1.5 h
  7. custompurified via preparative reversed phase HPLC (gradient of methanol in water+0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-cdcd62c8116f47daabce59a311ac3107
Source dataset
uspto-grants-2014_07
Patent number
US08791272B2

Reaction notes

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