1,4-Dioxane → HCID 58994547, compound

HRID 1508114Notes

Reaction equation

HRID 1508114 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([NH:11][CH2:12][CH2:13][N:14]([CH3:16])[CH3:15])=[O:10])=[CH:4][C:3]=1Br.C1(P(C2CCCCC2)C2C=CC=C[C:26]=2[C:31]2[C:36](OC)=[CH:35][CH:34]=[CH:33][C:32]=2OC)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O1CCOC[CH2:56]1>CCOC(C)=O.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]>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([NH:11][CH2:12][CH2:13][N:14]([CH3:16])[CH3:15])=[O:10])=[CH:4][C:3]=1[C:34]1[CH2:33][CH2:32][C:31]([CH3:26])([CH3:56])[CH2:36][CH:35]=1

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 58994585HCID 58994585, compound

Product 1

HCID 58994547HCID 58994547, compoundYield 28%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a flask containing 2-(4-amino-3-bromo-phenyl)-N-(2-dimethylamino-ethyl)-acetamide (as prepared in the previous step, 83 mg, 0.27 mmol), tris(dibenzylideneacetone)dipalladium (0) (4.0 mg, 0.0080 mmol), 2-(dicyclohexylphosphino)-2′,6′-dimethoxy-1,1′-biphenyl (5.6 mg, 0.010 mmol) and K3PO4 (0.17 g, 0.82 mmol) was charged dioxane (3 mL) and the reaction was heated to 100° C. for 48 h. At this time the reaction was diluted with EtOAc (25 mL) and washed with water (25 mL). The organic layer was dried (Na2SO4) and concentrated in vacuo. The crude residue was purified by preparative TLC (10% MeOH—CHCl3) to afford 26 mg (28%) of the title compound as a tan solid. 1H-NMR (CDCl3; 400 MHz): δ 6.85 (dd, 1H, J=8.0, 2.1 Hz), 6.79 (d, 1H, J=2.1 Hz), 6.59 (d, 1H, J=8.0 Hz), 6.01 (br s, 1H), 5.60 (m, 1H), 3.66 (br s, 2H), 3.35 (s, 2H), 3.23-3.18 (m, 2H), 2.27 (t, 1H, J=6.1 Hz), 2.20-2.14 (m, 2H), 2.09 (s, 6H), 1.90-1.88 (m, 2H), 1.44 (t, 2H, J=6.3 Hz), 0.92 (s, 6H).

Workup

  1. washwashed with water (25 mL)
  2. dry with materialThe organic layer was dried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. customThe crude residue was purified by preparative TLC (10% MeOH—CHCl3)

Sources & evidence

ORD record
ord-db68b4a15c7c4fbdad4908f937a2fc1b
Source dataset
uspto-grants-2015_12
Patent number
US09221797B2

Reaction notes

Loading…