tert-Butyl carbazate → 1h-Indazole-5-carboxylic acid,1-acetyl-3-(4-fluorophenyl)-

HRID 1349764Notes

Reaction equation

HRID 1349764 reaction equation
C(OC(C)(C)C)(=[O:4])NN.[C:10]([N:13]1[C:21]2[C:16](=[CH:17][C:18]([C:22](Cl)=[O:23])=[CH:19][CH:20]=2)[C:15]([C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)=[N:14]1)(=[O:12])[CH3:11]>N1C=CC=CC=1>[C:10]([N:13]1[C:21]2[C:16](=[CH:17][C:18]([C:22]([OH:4])=[O:23])=[CH:19][CH:20]=2)[C:15]([C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)=[N:14]1)(=[O:12])[CH3:11]

Participants

4

Reactant 2

HCID 70091tert-Butyl carbazateHCID 224802271-acetyl-3-(4-fluorophenyl)-1H-indazole-5-carbonyl chloride

Product 1

HCID 224798881h-Indazole-5-carboxylic acid,1-acetyl-3-(4-fluorophenyl)-

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a solution containing tert-butyl carbazate (0.79 g, 0.006 mol) in pyridine (30 mL) was added 1-acetyl-3-(4-fluorophenyl)-1H-indazole-5-carbonyl chloride (1.7 g, 0.005 mol). The reaction mixture was allowed to stir at ambient temperature for 18 hours. Solvent was removed and water was added to the mixture. The reaction was extracted with ethyl acetate. Some 1-acetyl-3-(4-fluorophenyl)-1H-indazole-5-carboxylic acid was isolated. The reaction mixture was treated with an equivalent of tert-butyl carbazate and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride in dichloromethane and allowed to stir overnight. The reaction was extracted with ethyl acetate. The product was taken up in a solution of 0.3% ammonia in methanol (˜50 mL) and allowed to stir overnight. The reaction mixture was extracted with dichloromethane, dried with magnesium sulfate, and concentrated. The material was purified by silica gel chromatography using 2% methanol in dichloromethane. The product was taken up in ethanol and gaseous hydrochloric acid was bubbled into solution. A solid precipitated out and was collected by filtration. This material was dried to provide the title compound (0.91 g, 56% yield). ES-MS (m/z) 271 [M+1]+.

Workup

  1. customSolvent was removed
  2. additionwater was added to the mixture
  3. extractionThe reaction was extracted with ethyl acetate

Sources & evidence

ORD record
ord-dfa4f628f15b4777b2694331f3a5fc8a
Source dataset
uspto-grants-2007_05
Patent number
US07211594B2

Reaction notes

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