Aniline → HCID 54373276, compound

HRID 1385093Notes

Reaction equation

HRID 1385093 reaction equation
S(Cl)(Cl)=O.[CH:5]1([N:10]2[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([C:19]([OH:21])=O)[CH:17]=3)[C:12]([CH2:22][CH3:23])=[N:11]2)[CH2:9][CH2:8][CH2:7][CH2:6]1.[NH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(N(CC)CC)C>C1(C)C=CC=CC=1.C(Cl)Cl.C(OCC)(=O)C.CN(C=O)C>[C:25]1([NH:24][C:19]([C:16]2[CH:17]=[C:18]3[C:13]([C:12]([CH2:22][CH3:23])=[N:11][N:10]3[CH:5]3[CH2:6][CH2:7][CH2:8][CH2:9]3)=[CH:14][CH:15]=2)=[O:21])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

9

Reactant 4

HCID 6115AnilineHCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 15545851HCID 15545851, compound

Product 1

HCID 54373276HCID 54373276, compoundYield 111.5%

Reagents, catalysts & solvents 4

HCID 1140TolueneSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

46 μL (0.629 mmol, 1.3 equiv) thionyl chloride were added to room temperature solution of 125 mg (0.484 mmol, 1.0 equiv) 1-cyclopentyl-3-ethyl-1H-indazole-6-carboxylic acid and 5 μL DMF in 5 mL anhydrous toluene. The reaction mixture was heated to reflux for 2 h, then cooled to room temperature, concentrated to dryness on a rotary evaporator, and dried at high vacuum, room temperature for several hours. The crude acid chloride was dissolved in 5 mL CH2Cl2 and added to a room temperature solution of 49 μL (0.532 mmol, 1.1 equiv) aniline and 67 μL (0.484 mmol, 1.0 equiv) triethylamine in 5 mL CH2Cl2. After 18 h at room temperature, the reaction mixture was diluted with 75 mL ethyl acetate, washed 1×15 mL each 1N HCl, H2O, brine, and dried over Na2SO4. Filtration, concentration of filtrate and drying gave 180 mg of an amber oil, which was purified on a silica gel column to give 160 mg of an off-white solid. Crystallization from ethyl acetate/hexanes gave 130 mg (81%) of a white crystalline solid: mp 146-147° C.; Anal. calcd for C21H23N3O: C, 75.65; H, 6.95; N, 12.60. Found: C, 75.65; H, 7.03; N, 12.55.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 2 h
  3. concentrationconcentrated to dryness on a rotary evaporator
  4. customdried at high vacuum, room temperature for several hours
  5. dissolutionThe crude acid chloride was dissolved in 5 mL CH2Cl2
  6. washwashed 1×15 mL each 1N HCl, H2O, brine
  7. dry with materialdried over Na2SO4
  8. filtrationFiltration, concentration of filtrate
  9. customdrying

Sources & evidence

ORD record
ord-331fd2fcf99a44d09a3e023e0af97a6f
Source dataset
uspto-grants-2001_07
Patent number
US06262040B1

Reaction notes

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