Potassium Carbonate → 9-tert-butyl-3-methoxy-2-pyridin-3-yl-14-(1,3-thiazol-5-yl)-5,6,10,11,12,13-hexahydroazocino[4',3':4,5]pyrrolo[2,1-a]isoquinolin-8(9H)-one

HRID 1971693Notes

Reaction equation

HRID 1971693 reaction equation
Br[C:2]1[C:3]([O:31][CH3:32])=[CH:4][C:5]2[CH2:6][CH2:7][N:8]3[C:14]4[C:15](=[O:25])[N:16]([C:21]([CH3:24])([CH3:23])[CH3:22])[CH2:17][CH2:18]O[CH2:20][C:13]=4[C:12]([C:26]4[S:30][CH:29]=[N:28][CH:27]=4)=[C:9]3[C:10]=2[CH:11]=1.B(O)(O)[C:34]1[CH:39]=[CH:38][CH:37]=[N:36][CH:35]=1.[C:42]([O-])([O-])=O.[K+].[K+].[OH-].[Na+]>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(COC)OC>[C:21]([N:16]1[CH2:17][CH2:18][CH2:42][CH2:20][C:13]2[C:12]([C:26]3[S:30][CH:29]=[N:28][CH:27]=3)=[C:9]3[C:10]4[CH:11]=[C:2]([C:34]5[CH:35]=[N:36][CH:37]=[CH:38][CH:39]=5)[C:3]([O:31][CH3:32])=[CH:4][C:5]=4[CH2:6][CH2:7][N:8]3[C:14]=2[C:15]1=[O:25])([CH3:23])([CH3:22])[CH3:24]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 27343783-Pyridinylboronic acidHCID 581248172-bromo-9-tert-butyl-3-methoxy-14-(1,3-thiazol-5-yl)-5,6,10,11-tetrahydro-9H-[1,4]oxazocino[7',6':4,5]pyrrolo[2,1-a]isoquinolin-8(13H)-one

Product 1

HCID 509063619-tert-butyl-3-methoxy-2-pyridin-3-yl-14-(1,3-thiazol-5-yl)-5,6,10,11,12,13-hexahydroazocino[4',3':4,5]pyrrolo[2,1-a]isoquinolin-8(9H)-oneYield 88.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

A degassed solution of 40 mg of 11i, 20 mg of pyridyl-3-boronic acid, 30 mg of K2CO3, 12 mg Pd(PPh3)4 and 3 ml of 90% aq. dimethoxyethane was heated at 90° C. for 16 hr. The reaction mixture was cooled, poured into 20 ml of 1N NaOH and extracted with ethyl acetate. The organic layer was washed with water, dried, concentrated and the residues were passed through a short silica column, using a gradient of toluene/acetone as eluent. The isolated material was treated with diethyl ether and gave 35 mg of 11j as white crystals; Mp: 227-229° C.; Rf 0.35 (toluene/acetone 1/1).

Workup

  1. temperatureThe reaction mixture was cooled
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with water
  4. customdried
  5. concentrationconcentrated
  6. additionThe isolated material was treated with diethyl ether

Sources & evidence

ORD record
ord-ae424c688ee146afb987c10b99e7650b
Source dataset
uspto-grants-2013_04
Patent number
US08431564B2

Reaction notes

Loading…