Ammonium Chloride → 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,2,3-trimethylbutanamide

HRID 218175Notes

Reaction equation

HRID 218175 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([C:17]([CH3:25])([CH3:24])[C:18]([CH3:23])([CH3:22])[C:19](O)=[O:20])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[Cl-].[NH4+].O[N:29]1C2N=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(C(C)C)CC)(C)C>C(OCC)(=O)C.C(#N)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([C:17]([CH3:25])([CH3:24])[C:18]([CH3:23])([CH3:22])[C:19]([NH2:29])=[O:20])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 670063023-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,2,3-trimethylbutanoic acid

Product 1

HCID 687047833-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,2,3-trimethylbutanamideYield 74%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred mixture of 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,2,3-trimethylbutanoic acid (230 mg; 0.68 mmol), ammonium chloride (180 mg, 3.4 mmol), 1-hydroxy-7-azabenzotriazole (92 mg, 0.68 mmol), anhydrous acetonitrile (5 mL), and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (325 mg, 1.7 mml) was added diisopropylethylamine (0.47 mL, 2.7 mmol). The mixture was stirred under nitrogen at rt for 22 hr before concentrated in vacuo. The residue was mixed with saturated aqueous sodium bicarbonate solution (15 mL) and extracted with dichloromethane (2×10 mL). The combined dichloromethane extracts were dried (Na2SO4). Flash chromatography (SiO2 Column, 10-100% ethyl acetate in hexanes) gave 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,2,3-trimethylbutanamide (169 mg, 0.50 mmol, 74% yield) as a white solid.

Workup

  1. concentrationbefore concentrated in vacuo
  2. additionThe residue was mixed with saturated aqueous sodium bicarbonate solution (15 mL)
  3. extractionextracted with dichloromethane (2×10 mL)
  4. dry with materialThe combined dichloromethane extracts were dried (Na2SO4)

Sources & evidence

ORD record
ord-027168a0aad74b139f6c0738a22d0042
Source dataset
uspto-grants-2012_06
Patent number
US08198311B2

Reaction notes

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