Sodium Carbonate → N-[1-[3',4'-bis(methyloxy)-4-biphenylyl]-2-(1-pyrrolidinyl)ethyl]-2-(6,7-dichloro-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)-N-methylacetamide

HRID 2114338Notes

Reaction equation

HRID 2114338 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([N:15]([CH3:32])[C:16](=[O:31])[CH2:17][N:18]2[C:23]3[CH:24]=[C:25]([Cl:29])[C:26]([Cl:28])=[CH:27][C:22]=3[O:21][CH2:20][C:19]2=[O:30])[CH2:9][N:10]2[CH2:14][CH2:13][CH2:12][CH2:11]2)=[CH:4][CH:3]=1.[CH3:33][O:34][C:35]1[CH:36]=[C:37](B(O)O)[CH:38]=[CH:39][C:40]=1[O:41][CH3:42].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]>[CH3:33][O:34][C:35]1[CH:36]=[C:37]([C:2]2[CH:7]=[CH:6][C:5]([CH:8]([N:15]([CH3:32])[C:16](=[O:31])[CH2:17][N:18]3[C:23]4[CH:24]=[C:25]([Cl:29])[C:26]([Cl:28])=[CH:27][C:22]=4[O:21][CH2:20][C:19]3=[O:30])[CH2:9][N:10]3[CH2:11][CH2:12][CH2:13][CH2:14]3)=[CH:4][CH:3]=2)[CH:38]=[CH:39][C:40]=1[O:41][CH3:42]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27347023,4-Dimethoxyphenylboronic acidHCID 57488849N-[1-(4-bromophenyl)-2-(1-pyrrolidinyl)ethyl]-2-(6,7-dichloro-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)-N-methylacetamide

Product 1

HCID 46847806N-[1-[3',4'-bis(methyloxy)-4-biphenylyl]-2-(1-pyrrolidinyl)ethyl]-2-(6,7-dichloro-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)-N-methylacetamideYield 39%

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-(1-pyrrolidinyl)ethyl]-2-(6,7-dichloro-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)-N-methylacetamide (70 mg, 0.13 mmol) and 3,4-dimethoxyphenylboronic acid (26 mg, 0.14 mmol) in DMF (1 mL) was added Pd(dppf)Cl2 (5.3 mg, 0.0065 mmol) followed by 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 polypropylene filter and purified by Gilson Preparation HPLC (Xterra Prep RP, 19×150 mm, 18 mL/min, PH 10 with NH4OH, A: acetonitrile B: water, A: 40 to 99% over 15 min, UV detection at 214 nm) to give 30.1 mg (39%) of the title compound as an off white solid. MS (ES) m/e 598.1 [M+H]+.

Workup

  1. filtrationThe mixture was filtered through a 0.45 um polypropylene
  2. filtrationfilter
  3. custompurified by Gilson Preparation HPLC (Xterra Prep RP, 19×150 mm, 18 mL/min, PH 10 with NH4OH

Sources & evidence

ORD record
ord-d9068a3bb0714fd68f57cbd2e971a2f6
Source dataset
uspto-grants-2008_10
Patent number
US07432258B2

Reaction notes

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