4-Chlorobenzaldehyde → {1-[4-(4-Chloro-benzylamino)-benzyl]-3,5-dimethyl-1H-pyrazol-4-yl}-acetic acid

HRID 1631913Notes

Reaction equation

HRID 1631913 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].[Cl:21][C:22]1[CH:29]=[CH:28][C:25]([CH:26]=O)=[CH:24][CH:23]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>O1CCCC1>[Cl:21][C:22]1[CH:29]=[CH:28][C:25]([CH2:26][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)=[CH:24][CH:23]=1

Participants

5

Reactant 3

HCID 77264-ChlorobenzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 66707335[1-(4-aminobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl]acetic acid methyl ester2×

Product 1

HCID 58071766{1-[4-(4-Chloro-benzylamino)-benzyl]-3,5-dimethyl-1H-pyrazol-4-yl}-acetic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Reductive amination: To a solution of [1-(4-amino-benzyl)-3,5-dimethyl-1H-pyrazol-4-yl]-acetic acid methyl ester (intermediate 1.1.3, 100 mg, 0.37 mmol) in tetrahydrofurane (1 mL) was added 4-chlorobenzaldehyde (185 mg, 1.32 mmol) and sodium triacetoxyborohydride (240 mg, 1.13 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, 0.6 mL). After 4 h, the mixture was neutralized 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, 0.6 mL)
  6. waitAfter 4 h
  7. custompurified via preparative reversed phase HPLC (gradient of methanol in water+0.1% NH3)

Sources & evidence

ORD record
ord-568c89e330a145c4a330b2e478ec25ce
Source dataset
uspto-grants-2014_07
Patent number
US08791272B2

Reaction notes

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