Urea → {1-[4-(3-Benzyl-ureido)-benzyl]-3,5-dimethyl-1H-pyrazol-4-yl}-acetic acid

HRID 1631911Notes

Reaction equation

HRID 1631911 reaction equation
NC(N)=O.C[O:6][C:7](=[O:24])[CH2:8][C:9]1[C:10]([CH3:23])=[N:11][N:12]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][CH:17]=2)[C:13]=1[CH3:14].[CH2:25]([N:32]=[C:33]=[O:34])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>ClCCl>[CH2:25]([NH:32][C:33](=[O:34])[NH:22][C:19]1[CH:20]=[CH:21][C:16]([CH2:15][N:12]2[C:13]([CH3:14])=[C:9]([CH2:8][C:7]([OH:6])=[O:24])[C:10]([CH3:23])=[N:11]2)=[CH:17][CH:18]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

5

Reactant 3

HCID 1176UreaHCID 76639Benzyl isocyanateHCID 66707335[1-(4-aminobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl]acetic acid methyl ester2×

Product 1

HCID 58071673{1-[4-(3-Benzyl-ureido)-benzyl]-3,5-dimethyl-1H-pyrazol-4-yl}-acetic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Urea formation: To a solution of [1-(4-amino-benzyl)-3,5-dimethyl-1H-pyrazol-4-yl]-acetic acid methyl ester (intermediate 1.1.3, 160 mg, 0.59 mmol) in dichloromethane (2 mL) was added benzyl isocyanate (94 μL, 0.76 mmol). The reaction mixture was stirred for 1 h at room temperature. Saponification: After removing the volatiles under reduced pressure, the remaining residue was dissolved in methanol (1 mL) and treated with aqueous LiOH solution (1 M, 1.5 mL). After 18 h, the mixture was neutralized and purified via preparative reversed phase HPLC (gradient of methanol in water+0.1% NH3).

Workup

  1. customSaponification: After removing the volatiles under reduced pressure
  2. dissolutionthe remaining residue was dissolved in methanol (1 mL)
  3. additiontreated with aqueous LiOH solution (1 M, 1.5 mL)
  4. waitAfter 18 h
  5. custompurified via preparative reversed phase HPLC (gradient of methanol in water+0.1% NH3)

Sources & evidence

ORD record
ord-4a7ed20466de486f8028e39a15efbba4
Source dataset
uspto-grants-2014_07
Patent number
US08791272B2

Reaction notes

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