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

HRID 2354344Notes

Reaction equation

HRID 2354344 reaction equation
Br[C:2]1[CH:3]=[C:4]([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:5]=[CH:6][CH:7]=1.[N:34]1([C:40]([C:42]2[CH:43]=[C:44](B(O)O)[CH:45]=[CH:46][CH:47]=2)=[O:41])[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1.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]>[NH4+:10].[OH-:13].[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:4]3[CH:3]=[C:2]([C:46]4[CH:45]=[CH:44][CH:43]=[C:42]([C:40]([N:34]5[CH2:35][CH2:36][CH2:37][CH2:38][CH2:39]5)=[O:41])[CH:47]=4)[CH:7]=[CH:6][CH:5]=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

7

Reactant 3

HCID 10340Sodium CarbonateHCID 24901767B-(3-(1-Piperidinylcarbonyl)phenyl)boronic acidHCID 57457162N-[1-(3-bromophenyl)-2-(4-morpholinyl)ethyl]-2-(6,7-dichloro-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)-N-methylacetamide

Product 2

HCID 14923Ammonium HydroxideHCID 468479192-(6,7-dichloro-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)-N-methyl-N-{2-(4-morpholinyl)-1-[3'-(1-piperidinylcarbonyl)-3-biphenylyl]ethyl}acetamideYield 151.2%

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-(3-bromophenyl)-2-(4-morpholinyl)ethyl]-2-(6,7-dichloro-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)-N-methylacetamide (75.0 mg, 0.13 mmol) and [3-(1-piperidinylcarbonyl)phenyl]boronic acid (35.0 mg, 0.15 mmol) in DMF (1.5 mL) was added Pd(dppf)Cl2 (5.5 mg, 0.0067 mmol) and a 2M 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 was purified using a Gilson preparative HPLC (Xterra Prep RP, 30×100 mm, 45 mL/min, A: acetonitrile B: water, A: 30 to 70% over 10 min, PH 10 with NH4OH, UV detection at 214 nm) to give 65.4 mg (76%) of the title compound as off white solid. MS (ES) m/e 665.3 [M+H]+.

Workup

  1. filtrationThe mixture was filtered through a 0.45 uM
  2. filtrationfilter
  3. customwas purified

Sources & evidence

ORD record
ord-4cf0c4980dc54afd8adaeea93483741e
Source dataset
uspto-grants-2010_07
Patent number
US07749998B2

Reaction notes

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