8-Aminoquinoline → N-quinolin-8-ylquinolin-6-amine

HRID 1181181Notes

Reaction equation

HRID 1181181 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2.Br[C:13]1[CH:14]=[C:15]2[C:20](=[CH:21][CH:22]=1)[N:19]=[CH:18][CH:17]=[CH:16]2.CC(C)([O-])C.[Na+]>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].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(C)C=CC=CC=1>[N:10]1[C:11]2[C:6](=[CH:5][CH:4]=[CH:3][C:2]=2[NH:1][C:13]2[CH:14]=[C:15]3[C:20](=[CH:21][CH:22]=2)[N:19]=[CH:18][CH:17]=[CH:16]3)[CH:7]=[CH:8][CH:9]=1

Participants

7

Reactant 3

HCID 113598-AminoquinolineHCID 792436-BromoquinolineHCID 23676156Sodium t-butoxide

Product 1

HCID 58899094N-quinolin-8-ylquinolin-6-amineYield 55.9%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

To a flask equipped with a magnetic stirrer, reflux condensor, and nitrogen inlet was added 8-aminoquinoline (4.2 grams, 29.0 mmoles), 6-bromoquinoline (6.0 grams, 29.0 mmoles), tris(dibenzylideneacetone)dipalladium (0) (0.4 grams, 0.48 mmoles), rac-2,2′-bis(diphenylphosphino)-1,1′-binapthyl (0.6 grams, 0.60 mmoles), sodium tert-butoxide (4.7 grams, 49.0 mmoles) and anhydrous toluene (80 mL). The contents of the flask were refluxed for three days; cooled to room temperature; and filtered through a pad of silica gel. The silica gel pad was then eluted with dichloromethane (60 mL) and ethyl acetate (60 mL). The combined organic layers were concentrated in vacuo to yield a yellow solid. The solid was chromatographed on silica gel, eluting with a hexane/ethyl acetate gradient to afford 4.4 grams of the desired product as a yellow solid. 1H NMR (CDCl3) δ 8.8 (d, 2H), 8.6 (bs, 1H), 8.0-8.2 (m, 3H), 7.2-7.8 (m, 7H).

Workup

  1. customTo a flask equipped with a magnetic stirrer
  2. temperaturereflux condensor, and nitrogen inlet
  3. temperatureThe contents of the flask were refluxed for three days
  4. filtrationand filtered through a pad of silica gel
  5. washThe silica gel pad was then eluted with dichloromethane (60 mL) and ethyl acetate (60 mL)
  6. concentrationThe combined organic layers were concentrated in vacuo
  7. customto yield a yellow solid
  8. customThe solid was chromatographed on silica gel
  9. washeluting with a hexane/ethyl acetate gradient

Sources & evidence

ORD record
ord-0bb1daf18d6244f2a934c22f2c72790e
Source dataset
uspto-grants-2007_10
Patent number
US07285518B2

Reaction notes

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