Ethyl 4-bromobenzoate → Ethyl 4-{{4-[2-(11-ethyl-6,11-dihydro-5-methyl-6-oxo-5h-dipyrido[3,2-b:2',3'-e][1,4]diazepin-8-yl)ethoxy]-3-methylphenyl}amino}benzoate

HRID 393298Notes

Reaction equation

HRID 393298 reaction equation
[CH2:1]([N:3]1[C:9]2[N:10]=[CH:11][C:12]([CH2:14][CH2:15][O:16][C:17]3[CH:22]=[CH:21][C:20]([NH2:23])=[CH:19][C:18]=3[CH3:24])=[CH:13][C:8]=2[C:7](=[O:25])[N:6]([CH3:26])[C:5]2[CH:27]=[CH:28][CH:29]=[N:30][C:4]1=2)[CH3:2].Br[C:32]1[CH:42]=[CH:41][C:35]([C:36]([O:38][CH2:39][CH3:40])=[O:37])=[CH:34][CH:33]=1.C(O[Na])(C)(C)C.C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1.CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:1]([N:3]1[C:9]2[N:10]=[CH:11][C:12]([CH2:14][CH2:15][O:16][C:17]3[CH:22]=[CH:21][C:20]([NH:23][C:32]4[CH:42]=[CH:41][C:35]([C:36]([O:38][CH2:39][CH3:40])=[O:37])=[CH:34][CH:33]=4)=[CH:19][C:18]=3[CH3:24])=[CH:13][C:8]=2[C:7](=[O:25])[N:6]([CH3:26])[C:5]2[CH:27]=[CH:28][CH:29]=[N:30][C:4]1=2)[CH3:2]

Participants

8

Reactant 4

HCID 22043Ethyl 4-bromobenzoateHCID 634876Binap, (A+-)-HCID 2264885811-ethyl-5,11-dihydro-8-[2-(4-amino-2-methylphenoxy)ethyl]-5-methyl-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-oneHCID 178418730sodium 2-methylpropan-2-olate

Product 1

HCID 22648876Ethyl 4-{{4-[2-(11-ethyl-6,11-dihydro-5-methyl-6-oxo-5h-dipyrido[3,2-b:2',3'-e][1,4]diazepin-8-yl)ethoxy]-3-methylphenyl}amino}benzoateYield 40%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
105 °C

Procedure

A degassed mixture of 11-ethyl-5,11-dihydro-8-[2-(4-amino-2-methylphenoxy)ethyl]-5-methyl-6H-dipyrido[3,2-b:2′,3′-e][1,4]diazepin-6-one (100 mg, 0.25 mmol), ethyl 4-bromobenzoate (61.0 μL, 0.37 mmol), t-BuONa (36.0 mg, 0.37 mmol), Pd2(dba)3 (2.5 mg, 2.7 μmol) and (+/−)-BINAP (5.0 mg, 8.0 1mol) in toluene (8 mL) was heated to 105° C. under nitrogen for 48 h. The cooled reaction mixture was diluted with EtOAc, filtered through a short pad of diatomaceous earth and was concentrated under reduced pressure. The residue was purified by flash chromatography (Hexane:EtOAc, 1:1) to give the title compound (55 mg, 40% yield) as a white solid.

Workup

  1. customThe cooled reaction mixture
  2. filtrationfiltered through a short pad of diatomaceous earth
  3. concentrationwas concentrated under reduced pressure
  4. customThe residue was purified by flash chromatography (Hexane:EtOAc, 1:1)

Sources & evidence

ORD record
ord-fd40204fe0fd4cae9da61a2ce2d7ae93
Source dataset
uspto-grants-2004_10
Patent number
US06806265B2

Reaction notes

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