Carbamate → [1-(4-Benzyloxycarbonylamino-benzyl)-3,5-dimethyl-1H-pyrazol-4-yl]-acetic acid

HRID 1631909Notes

Reaction equation

HRID 1631909 reaction equation
C(=O)([O-])N.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].C(N(C(C)C)CC)(C)C.Cl[C:35]([O:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)=[O:36]>ClCCl>[CH2:38]([O:37][C:35]([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)=[O:36])[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1

Participants

6

Reactant 4

HCID 276CarbamateHCID 10387Benzyl chloroformateHCID 81531DiisopropylethylamineHCID 66707335[1-(4-aminobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl]acetic acid methyl ester2×

Product 1

HCID 58071822[1-(4-Benzyloxycarbonylamino-benzyl)-3,5-dimethyl-1H-pyrazol-4-yl]-acetic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Carbamate formation: To a solution of [1-(4-amino-benzyl)-3,5-dimethyl-1H-pyrazol-4-yl]-acetic acid methyl ester (intermediate 1.1.3, 70 mg, 0.26 mmol) in dichloromethane (1 mL) was added diisopropylethylamine (55 μL, 0.32 mmol) and benzyl chloroformate (55 μL, 0.39 mmol). The reaction mixture was stirred for 18 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 (1 mL) and treated with aqueous NaOH solution (4 M, 0.2 mL). The mixture was neutralized with aqueous HCl and purified via preparative reversed phase HPLC (gradient of methanol in water+0.1% NH3).

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 (1 mL)
  5. additiontreated with aqueous NaOH solution (4 M, 0.2 mL)
  6. custompurified via preparative reversed phase HPLC (gradient of methanol in water+0.1% NH3)

Sources & evidence

ORD record
ord-2114bd78b75a42618835725ec89b869f
Source dataset
uspto-grants-2014_07
Patent number
US08791272B2

Reaction notes

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