Potassium Carbonate → 9-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

HRID 1971705Notes

Reaction equation

HRID 1971705 reaction equation
[C:1]([N:5]1[CH2:26][CH2:25][CH2:24][C:8]2[C:9]([Br:23])=[C:10]3[C:19]4[CH:18]=[C:17](Br)[C:16]([O:21][CH3:22])=[CH:15][C:14]=4[CH2:13][CH2:12][N:11]3[C:7]=2[C:6]1=[O:27])([CH3:4])([CH3:3])[CH3:2].[N:28]1[CH:33]=[CH:32][CH:31]=[C:30](B(O)O)[CH:29]=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[CH2:26][CH2:25][CH2:24][C:8]2[C:9]([Br:23])=[C:10]3[C:19]4[CH:18]=[C:17]([C:30]5[CH:29]=[N:28][CH:33]=[CH:32][CH:31]=5)[C:16]([O:21][CH3:22])=[CH:15][C:14]=4[CH2:13][CH2:12][N:11]3[C:7]=2[C:6]1=[O:27])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27343783-Pyridinylboronic acidHCID 58124863HCID 58124863, compound

Product 1

HCID 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-oneYield 63.6%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
90 °C

Procedure

A mixture of 150 mg of 13c, 44 mg of pyridine-3-boronic acid, 80 mg of K2CO3 and 22 mg of Pd(PPh3)4 in 3 ml of degassed dimethoxyethane was heated at 90° C., for 16 hr. The reaction mixture was cooled and diluted with 20 ml of 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 crude material was chromatographed over silica gel, using a gradient of heptane/ethyl acetate as eluent. The product isolated was triturated with pentane, to provide 95 mg of 13d as white, crystalline material. Mp 184-186° C. Rf 0.25 (heptane/ethyl acetate 1/1). MS-ESI: [M+1] 494.11 and 496.11.

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 crude material was chromatographed over silica gel
  7. customThe product isolated
  8. customwas triturated with pentane

Sources & evidence

ORD record
ord-e8e9c5c49dcf4673bfb513d023630da4
Source dataset
uspto-grants-2013_04
Patent number
US08431564B2

Reaction notes

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