Potassium Carbonate → 9-tert-butyl-2,13-di-(pyridin3-yl)-3-methoxy-5,6,9,10,11,12-hexahydro-8H-azepino[4',3':4,5]pyrrolo[2,1-a]isoquinolin-8-one

HRID 1971706Notes

Reaction equation

HRID 1971706 reaction equation
[C:1]([N:5]1[CH2:31][CH2:30][CH2:29][C:8]2[C:9](Br)=[C:10]3[C:19]4[CH:18]=[C:17]([C:20]5[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=5)[C:16]([O:26][CH3:27])=[CH:15][C:14]=4[CH2:13][CH2:12][N:11]3[C:7]=2[C:6]1=[O:32])([CH3:4])([CH3:3])[CH3:2].[N:33]1[CH:38]=[CH:37][CH:36]=[C:35](B(O)O)[CH:34]=1.C([O-])([O-])=O.[K+].[K+]>C(COC)OC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([N:5]1[CH2:31][CH2:30][CH2:29][C:8]2[C:9]([C:35]3[CH:34]=[N:33][CH:38]=[CH:37][CH:36]=3)=[C:10]3[C:19]4[CH:18]=[C:17]([C:20]5[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=5)[C:16]([O:26][CH3:27])=[CH:15][C:14]=4[CH2:13][CH2:12][N:11]3[C:7]=2[C:6]1=[O:32])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27343783-Pyridinylboronic acidHCID 581248219-tert-butyl-2-pyridin-3-yl-13-bromo-3-methoxy-5,6,9,10,11,12-hexahydro-8H-azepino[4',3':4,5]pyrrolo[2,1-a]isoquinolin-8-one

Product 1

HCID 581247989-tert-butyl-2,13-di-(pyridin3-yl)-3-methoxy-5,6,9,10,11,12-hexahydro-8H-azepino[4',3':4,5]pyrrolo[2,1-a]isoquinolin-8-oneYield 69.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 45 mg of 13d, 20 mg of pyridine-3-boronic acid, 30 mg of K2CO3 and 10 mg of Pd(PPh3)4 in 2 ml of degassed dimethoxyethane was heated at 90° C., for 16 hr. The reaction mixture was cooled, diluted with water and the product was extracted with ethyl acetate. The extract was washed once with 2N KOH and once with water, dried and concentrated. The residue was purified by chromatography over silica gel, using a gradient of toluene/acetone as eluent. The isolated product was triturated with diethyl ether, to provide 31 mg of 13e as white, crystalline material; Mp 310-312° C.

Workup

  1. temperatureThe reaction mixture was cooled
  2. extractionthe product was extracted with ethyl acetate
  3. washThe extract was washed once with 2N KOH and once with water
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was purified by chromatography over silica gel
  7. customThe isolated product was triturated with diethyl ether

Sources & evidence

ORD record
ord-112b4f0023774ec2990621a079fbac6a
Source dataset
uspto-grants-2013_04
Patent number
US08431564B2

Reaction notes

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