Sodium Carbonate → HCID 57488832, compound

HRID 2114350Notes

Reaction equation

HRID 2114350 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:47]=[CH:46][C:45](B(O)O)=[CH:44][CH:43]=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:45]4[CH:44]=[CH:43][C:42]([NH:41][C:39](=[O:40])[O:38][C:35]([CH3:36])([CH3:34])[CH3:37])=[CH:47][CH:46]=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 3613184(4-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 57488832HCID 57488832, compoundYield 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 (1.64 g, 2.9 mmol) and [4-({[(1,1-dimethylethyl)oxy]carbonyl}amino)phenyl]boronic acid (0.77 g, 3.2 mmol) in DMF (10 mL) was added Pd(dppf)Cl2 (0.12 g, 0.15 mmol) and 2N aqueous solution of Na2CO3 (0.26 mL, 0.52 mmol). The resultant mixture was stirred at 80° C. for 16 h. The mixture was filtered through a 0.45 uM filter and concentrated under reduce 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 recrystalized in methanol to give 0.77 g (40%) white solid. The mother liquid was concentrated and was purified by using a Gilson preparative HPLC (Phenomenex, 100×50 mm, 10 micron, 90 mL/min, A: acetonitrile B: water, A: 10 to 90% over 15 min, UV detection at 214 nm) to give 0.10 g (5%) of the title compound as yellow oil. Total yield 45%. MS (ES) m/e 669.4 [M+H]+.

Workup

  1. filtrationThe mixture was filtered through a 0.45 uM
  2. filtrationfilter
  3. concentrationconcentrated
  4. dissolutionThe residue was dissolved in ethyl acetate (100 mL)
  5. washwashed with 5% NaHCO3 (100 mL) and brine (100 mL)
  6. dry with materialThe organic layer was dried over MgSO4
  7. concentrationconcentrated
  8. customThe residue was recrystalized in methanol

Sources & evidence

ORD record
ord-c398dbd6cba84726b2ed3ef2a64a8f07
Source dataset
uspto-grants-2008_10
Patent number
US07432258B2

Reaction notes

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