Sodium Carbonate → 1,1-dimethylethyl {4'-[1-[[(6,7-dichloro-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetyl](methyl)amino]-2-(4-morpholinyl)ethyl]-3-biphenylyl}carbamate

HRID 2114430Notes

Reaction equation

HRID 2114430 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([N:16]([CH3:33])[C:17](=[O:32])[CH2:18][N:19]2[C:24]3[CH:25]=[C:26]([Cl:30])[C:27]([Cl:29])=[CH:28][C:23]=3[O:22][CH2:21][C:20]2=[O:31])[CH2:9][N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[CH:4][CH:3]=1.[CH3:34][C:35]([O:38][C:39]([NH:41][C:42]1[CH:43]=[C:44](B(O)O)[CH:45]=[CH:46][CH:47]=1)=[O:40])([CH3:37])[CH3:36].C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:30][C:26]1[C:27]([Cl:29])=[CH:28][C:23]2[O:22][CH2:21][C:20](=[O:31])[N:19]([CH2:18][C:17]([N:16]([CH3:33])[CH:8]([C:5]3[CH:6]=[CH:7][C:2]([C:46]4[CH:45]=[CH:44][CH:43]=[C:42]([NH:41][C:39](=[O:40])[O:38][C:35]([CH3:36])([CH3:34])[CH3:37])[CH:47]=4)=[CH:3][CH:4]=3)[CH2:9][N:10]3[CH2:15][CH2:14][O:13][CH2:12][CH2:11]3)=[O:32])[C:24]=2[CH:25]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2773228(3-Boc-aminophenyl)boronic acidHCID 57457161N-[1-(4-bromophenyl)-2-(4-morpholinyl)ethyl]-2-(6,7-dichloro-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)-N-methylacetamide

Product 1

HCID 574890281,1-dimethylethyl {4'-[1-[[(6,7-dichloro-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetyl](methyl)amino]-2-(4-morpholinyl)ethyl]-3-biphenylyl}carbamateYield 40%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of N-[1-(4-bromophenyl)-2-(4-morpholinyl)ethyl]-2-(6,7-dichloro-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)-N-methylacetamide (3.28 g, 5.8 mmol) and [3-({[(1,1-dimethylethyl)oxy]carbonyl}amino)phenyl]boronic acid (2.00 g, 8.4 mmol) in DMF (15 mL) was added Pd(dppf)Cl2 (0.24 g, 0.29 mmol) and 2N solution of Na2CO3 (11.6 mL, 23.2 mmol). The resultant mixture was stirred at 80° C. for 16 h. The mixture was filtered through a bed of celite and the filtrate was concentrated under reduced pressure. The residue was dissolved in ethyl acetate (100 mL) and washed with 5% NaHCO3 (100 mL) and brine (100 mL). The organic layer was dried over MgSO4 and concentrated. The residue was dissolved in methanol, and water was added to precipitate a tan solid. The solid was collected by filtration and air dried to give 1.55 g (40%) of the title compound a tan solid. MS (ES) m/e 669 [M+H]+

Workup

  1. filtrationThe mixture was filtered through a bed of celite
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. dissolutionThe residue was dissolved in ethyl acetate (100 mL)
  4. washwashed with 5% NaHCO3 (100 mL) and brine (100 mL)
  5. dry with materialThe organic layer was dried over MgSO4
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in methanol
  8. additionwater was added
  9. customto precipitate a tan solid
  10. filtrationThe solid was collected by filtration and air
  11. customdried

Sources & evidence

ORD record
ord-bfa274f5740c4355aab983a9f50bd4ad
Source dataset
uspto-grants-2008_10
Patent number
US07432258B2

Reaction notes

Loading…