Chlorotrimethylsilane → 2-[4-(4H-1,2,4-triazol-4-yl)phenyl]acetic acid

HRID 1453791Notes

Reaction equation

HRID 1453791 reaction equation
[CH:1]([NH:3][NH:4][CH:5]=O)=O.C[Si](Cl)(C)C.CCN(CC)CC.[NH2:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][C:27]([OH:29])=[O:28])=[CH:22][CH:21]=1>N1C=CC=CC=1>[N:4]1[N:3]=[CH:1][N:19]([C:20]2[CH:21]=[CH:22][C:23]([CH2:26][C:27]([OH:29])=[O:28])=[CH:24][CH:25]=2)[CH:5]=1

Participants

6

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 8471TriethylamineHCID 123421,2-HydrazinedicarboxaldehydeHCID 145334-Aminophenylacetic acid

Product 1

HCID 204742832-[4-(4H-1,2,4-triazol-4-yl)phenyl]acetic acidYield 93%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
100 °C

Procedure

Adapting a protocol by Catarzi et al (J. Med. Chem., 2001, 44, 3157-3165), diformylhydrazine (352 mg, 4.0 mmol) and then dropwise trimethylsilyl chloride (2.53 mL, 20 mmol) and Et3N (1.30 mL, 9.3 mmol) were added to a suspension of 4-aminophenylacetic acid (201 mg, 1.33 mmol) in anhydrous pyridine. The mixture was heated at 100° C. overnight, volatiles were removed at reduced pressure and the resulting solid was treated with water (6 mL), collected, washed with H2O and dried in vacuo to provide 251 mg (93%) of 141JP01 as a light brown solid. LCMS m/z 204[M+H]+. 1H-NMR (DMSO-d6) δ 9.05 (s, 2H), 7.62 (d, 1H, J=8.6), 7.40 (d, 1H, J=8.2), 3.61 (s, 2H).

Workup

  1. customvolatiles were removed at reduced pressure
  2. additionthe resulting solid was treated with water (6 mL)
  3. customcollected
  4. washwashed with H2O
  5. customdried in vacuo

Sources & evidence

ORD record
ord-95f550f9158f46e6a4088ee52ac3c84a
Source dataset
uspto-grants-2009_01
Patent number
US07476682B2

Reaction notes

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