4-Aminoacetanilide → HCID 24877275, compound

HRID 333406Notes

Reaction equation

HRID 333406 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5](/[C:6](=[C:12]3\[O:13][C:14]([CH3:24])([CH3:23])[C:15]([N:17]4[CH2:22][CH2:21][O:20][CH2:19][CH2:18]4)=[CH:16]\3)/[C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1.N[C:26]1[CH:31]=[CH:30][C:29]([NH:32][C:33](=[O:35])[CH3:34])=[CH:28][CH:27]=1.C1(P(C2C=CC=CC=2C2C=CC=CC=2[N:61](C)C)C2CCCCC2)CCCCC1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:23][C:14]1([CH3:24])[O:13]/[C:12](=[C:6]2/[C:7](=[O:11])[NH:8][C:9]3[C:5]/2=[CH:4][CH:3]=[C:2]([NH:61][C:27]2[CH:28]=[C:29]([NH:32][C:33](=[O:35])[CH3:34])[CH:30]=[CH:31][CH:26]=2)[CH:10]=3)/[CH:16]=[C:15]1[N:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1

Participants

7

Reactant 4

HCID 312304-AminoacetanilideHCID 2733832Lithium HexamethyldisilazideHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 24964164HCID 24964164, compound

Product 1

HCID 24877275HCID 24877275, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
62 °C

Procedure

A 25 mL reaction flask was charged with (3E)-6-bromo-3-(5,5-dimethyl-4-morpholin-4-ylfuran-2(5H)-ylidene)-1,3-dihydro-2H-indol-2-one (100 mg, 0.26 mmol), N-(4-aminophenyl)acetamide (46 mg, 0.31 mmol), dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (4.9 mg, 0.012 mmol), Pd2(dba)3 (4.8 mg, 0.0052 mmol), 1M LiHMDS in THF (0.83 mL, 0.83 mmol) and dry THF (10 mL). The mixture was purged with nitrogen and heated in 62° C. bath under nitrogen for 2 hours. After cooling to room temperature, the reaction mixture was quenched with 0.5 mL of 2M HCl, and diluted with ethyl acetate (100 mL). The solution was washed with saturated NaHCO3 (2×50 mL), brine (50 mL), and concentrated to give the crude product. Purification of the crude product by silica gel chromatography with a gradient of methanol in chloroform (5-10%) led to N-(3-{[(3E)-3-(5,5-dimethyl-4-morpholin-4-ylfuran-2(5H)-ylidene)-2-oxo-2,3-dihydro-1H-indol-6-yl]amino}phenyl)acetamide as a yellow solid. Yield: 20 mg, 17%.

Workup

  1. customA 25 mL reaction flask
  2. customThe mixture was purged with nitrogen
  3. temperatureAfter cooling to room temperature
  4. customthe reaction mixture was quenched with 0.5 mL of 2M HCl
  5. additiondiluted with ethyl acetate (100 mL)
  6. washThe solution was washed with saturated NaHCO3 (2×50 mL), brine (50 mL)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-1dbdb6ce0e2646e0b8cb0c2b682c740a
Source dataset
uspto-grants-2014_11
Patent number
US08877923B2

Reaction notes

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