Dimethylformamide → 4-((3-aminophenyl)ethynyl)-1H-indazol-3-amine

HRID 589914Notes

Reaction equation

HRID 589914 reaction equation
CN(C=O)C.I[C:7]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:8]=1[C:9]([NH2:16])=[N:10][NH:11]2.[C:17]([C:19]1[CH:20]=[C:21]([CH:23]=[CH:24][CH:25]=1)[NH2:22])#[CH:18].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cu](I)I.C(N(CC)CC)C>[NH2:22][C:21]1[CH:20]=[C:19]([C:17]#[C:18][C:7]2[CH:15]=[CH:14][CH:13]=[C:12]3[C:8]=2[C:9]([NH2:16])=[N:10][NH:11]3)[CH:25]=[CH:24][CH:23]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 11776TriphenylphosphineHCID 104682Benzenamine, 3-ethynyl-HCID 40577874-iodo-1H-indazol-3-amine

Product 1

HCID 1186384254-((3-aminophenyl)ethynyl)-1H-indazol-3-amine

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 8471TriethylamineSolvent

Conditions

Temperature
60 °C

Procedure

To 8 ml of DMF was added 4-iodo-1H-indazol-3-amine (690 mg, 2.65 mmol) and 3-ethynylaniline (480 mg, 1.5 eq., 4.1 mmol). Following that, Bis(triphenylphosphine) palladium(II) dichloride (180 mg, 0.25 mmol, 10 mol %), Copper Iodide (100 mg, 0.52 mmol, 20 mol %), Triphenylphosphine (18 mg, 0.07 mmol, 3 mol %) and 8 ml of triethylamine was added. Nitrogen was bubbled through the reaction mixture for 15 minutes. The reaction was then set with a reflux condenser, set under nitrogen atmosphere, and heated at 60° C. for 2 hours. After that, the reaction was cooled to room temperature and 40 ml of ethyl acetate was added. The organic layer was extracted with aqueous sodium bicarbonate (3×40 ml), brine (3×40 ml), dried using anhydrous sodium sulfate, loaded onto silica and columned to give 4-((3-aminophenyl)ethynyl)-1H-indazol-3-amine.

Workup

  1. additionwas added
  2. customNitrogen was bubbled through the reaction mixture for 15 minutes
  3. customThe reaction was then set with a reflux condenser
  4. temperatureAfter that, the reaction was cooled to room temperature
  5. addition40 ml of ethyl acetate was added
  6. extractionThe organic layer was extracted with aqueous sodium bicarbonate (3×40 ml), brine (3×40 ml)
  7. customdried

Sources & evidence

ORD record
ord-e1fda866a7f34f3db769165eb6f574ac
Source dataset
uspto-grants-2016_01
Patent number
US09233968B1

Reaction notes

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