Sodium Carbonate → N-[2-(3,3-Dimethyl-but-1-enyl)-benzyloxy]-2-[(pyridin-4-ylmethyl)-amino]-benzamide

HRID 1663129Notes

Reaction equation

HRID 1663129 reaction equation
I[C:2]1[CH:26]=[CH:25][CH:24]=[CH:23][C:3]=1[CH2:4][O:5][NH:6][C:7](=[O:22])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[NH:14][CH2:15][C:16]1[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=1.[CH3:27][C:28]([CH3:35])([CH3:34])[CH:29]=[CH:30]B(O)O.C(=O)([O-])[O-].[Na+].[Na+].C([O-])(=O)C.[NH4+]>C1(C)C=CC=CC=1.[Pd].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.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>[CH3:27][C:28]([CH3:35])([CH3:34])[CH:29]=[CH:30][C:2]1[CH:26]=[CH:25][CH:24]=[CH:23][C:3]=1[CH2:4][O:5][NH:6][C:7](=[O:22])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[NH:14][CH2:15][C:16]1[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=1

Participants

7

Reactant 4

HCID 10340Sodium Carbonate2×HCID 517165Ammonium AcetateHCID 27632983,3-Dimethyl-1-butenylboronic acid2×HCID 11487973N-((2-iodobenzyl)oxy)-2-((pyridin-4-ylmethyl)amino)benzamide

Product 1

HCID 73096176N-[2-(3,3-Dimethyl-but-1-enyl)-benzyloxy]-2-[(pyridin-4-ylmethyl)-amino]-benzamideYield 94.8%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalyst2×HCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

Argon was bobbled through a mixture of N-(2-Iodo-benzyloxy)-2-[(pyridin-4-ylmethyl)-amino]-benzamide (example 360, 151 mg, 0.33 mmol) in toluene (20 ml) for 10 to 15 minutes. Tetrakis(triphenylphosphine) palladium (19 mg) was added and the mixture was stirred for 10 minutes before addition of 3,3-dimethyl-1-butenylboronic acid (Aldrich, 50 mg) and a degassed 2M solution of sodium carbonate (0.329 ml). The reaction flask (screw-cap) was sealed and the reaction mixture was heated to 120° C. for 3 hours. More tetrakis(triphenylphosphine) palladium (0.05 eq.), 2M sodium carbonate (0.329 ml), and 3,3-dimethyl-1-butenylboronic acid (50 mg) was added and stirring was continued at 120° C. over night. The mixture was cooled to room temperature and 25% ammonium acetate was added and stirring was continued for 10 min. The mixture was partitioned between EtOAc and water. The aqueous phase was extracted with EtOAc and the combined organic layers were washed with brine, dried (MgSO4) and evaporated under reduced pressure. The residue was subjected to chromatography on silica gel (elution with 1% methanol in dichloromethane v/v) and gave the title compound (130 mg). 13C-NMR (CDCl3) δ 168.9, 149.8, 149.1, 148.7, 145.1, 138.8, 133.4, 131.1, 129.2, 127.4, 126.8, 126.2, 122.0, 121.5, 115.7, 112.8, 112.0, 76.2, 46.1, 33.8, 29.6.

Workup

  1. customThe reaction flask (screw-cap)
  2. customwas sealed
  3. waitwas continued at 120° C. over night
  4. temperatureThe mixture was cooled to room temperature
  5. stirringstirring
  6. customThe mixture was partitioned between EtOAc and water
  7. extractionThe aqueous phase was extracted with EtOAc
  8. washthe combined organic layers were washed with brine
  9. dry with materialdried (MgSO4)
  10. customevaporated under reduced pressure
  11. washelution with 1% methanol in dichloromethane v/v) and

Sources & evidence

ORD record
ord-77987d5f2ecf49febc0670d69343d582
Source dataset
uspto-grants-2011_10
Patent number
US08034811B2

Reaction notes

Loading…