Toluene → HCID 69060302, compound

HRID 860106Notes

Reaction equation

HRID 860106 reaction equation
[Cl-].[NH4+:2].C[Al](C)C.C1(C)C=CC=CC=1.C[O:15][C:16]([C:18]1[NH:19][C:20]([C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([CH3:40])[N:35]=2)=[C:21]([C:23]2[CH:33]=[CH:32][C:26]3=[N:27][N:28]([CH2:30]C)[N:29]=[C:25]3[CH:24]=2)[N:22]=1)=O>C1C=CC=CC=1>[CH3:30][N:28]1[N:27]=[C:26]2[CH:32]=[CH:33][C:23]([C:21]3[N:22]=[C:18]([C:16]([NH2:2])=[O:15])[NH:19][C:20]=3[C:34]3[CH:39]=[CH:38][CH:37]=[C:36]([CH3:40])[N:35]=3)=[CH:24][C:25]2=[N:29]1

Participants

6

Reactant 4

HCID 1140TolueneHCID 25517Ammonium ChlorideHCID 16682925TrimethylaluminumHCID 69066172HCID 69066172, compound

Product 1

HCID 69060302HCID 69060302, compoundYield 17.1%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent2×

Conditions

Temperature
0 °C

Procedure

Suspension of ammonium chloride (12 mg, 0.21 mmol) in 2 ml dry benzene was cooled to 0° C. 2M solution of trimethylaluminum in toluene (105 μl, 0.21 mmol) was slowly added and the reaction warmed to room temperature and stirred for 2 hours. This suspension was added to separate suspension of 4-(2-ethyl-2H-benzotriazol-5-yl)-5-(6-methyl-pyridin-2-yl)-1H-imidazole-2-carboxylic acid methyl ester (25 mg, 0.07 mmol) (prepared according to procedures analogous to example 1) in 1 ml dry benzene and the reaction heated at 50° C. overnight. The reaction was quenched by the addition of excess 1M aqueous solution of hydrochloric acid. The reaction was extracted three times with chloroform. Mass spectrometry analysis of organic extracts show no presence of desired product. The remaining aqueous layer was concentrated to dryness. The aqueous extract reside was purified on Biotage Flash 12S silica gel column using chloroform/methanol gradient system (99:1 to 80:20, respectively) as eluent to afford 4-(2-methyl-2H-benzotriazol-5-yl)-5-(6-methyl-pyridin-2-yl)-1H-imidazole-2-carboxylic acid amide (4 mg, 16% yield). HPLC tR=3.70 min, LC-MS=344 (M+1).

Workup

  1. temperaturethe reaction warmed to room temperature
  2. additionThis suspension was added
  3. customto separate
  4. temperaturethe reaction heated at 50° C. overnight
  5. customThe reaction was quenched by the addition of excess 1M aqueous solution of hydrochloric acid
  6. extractionThe reaction was extracted three times with chloroform
  7. concentrationThe remaining aqueous layer was concentrated to dryness
  8. customThe aqueous extract reside was purified on Biotage Flash 12S silica gel column

Sources & evidence

ORD record
ord-c7087a8fe47f479888b10548dc340863
Source dataset
uspto-grants-2006_12
Patent number
US07153872B2

Reaction notes

Loading…