Potassium Phosphate, Tribasic → HCID 10164661, compound

HRID 2213842

Reaction equation

HRID 2213842 reaction equation
[CH2:1]([O:8][C:9]1[C:25]([O:26][CH3:27])=[CH:24][C:12]2[CH:13]=[C:14]3[C:19](=[CH:20][C:11]=2[CH:10]=1)[N:18]=[CH:17][C:16]([C:21]#[N:22])=[C:15]3Cl)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:28][C:29]1[CH:35]=[C:34]([F:36])[C:33]([O:37][CH3:38])=[CH:32][C:30]=1[NH2:31].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>COCCOC.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]([O:8][C:9]1[C:25]([O:26][CH3:27])=[CH:24][C:12]2[CH:13]=[C:14]3[C:19](=[CH:20][C:11]=2[CH:10]=1)[N:18]=[CH:17][C:16]([C:21]#[N:22])=[C:15]3[NH:31][C:30]1[CH:32]=[C:33]([O:37][CH3:38])[C:34]([F:36])=[CH:35][C:29]=1[Cl:28])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 21956464HCID 21956464, compoundHCID 219564782-Chloro-4-fluoro-5-methoxybenzenamine

Product 1

HCID 10164661HCID 10164661, compoundYield 36%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 8-(benzyloxy)-4-chloro-7-methoxybenzo[g]quinoline-3-carbonitrile (1.00 g, 2.7 mmol), 2-chloro-4-fluoro-5-methoxyaniline (560 mg, 3.2 mmol), tris(dibenzylideneacetone)dipalladium(0) (240 mg, 0.26 mmol), 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (330 mg, 0.84 mmol) and K3PO4 (860 mg, 4.1 mmol) in 15 mL of ethylene glycol dimethyl ether is heated at 80° C. for 3 hours. An additional 5% of all reagents is added and the mixture is heated at 80° C. for 2 hours then cooled to room temperature and partitioned between aqueous sodium bicarbonate and methylene chloride. The organic layer is dried over magnesium sulfate, filtered and concentrated in vacuo. Purification by column chromatography eluting with 1:1 hexane/ethyl acetate yields 500 mg (36%) of 8-(benzyloxy)-4-[(2-chloro-4-fluoro-5-methoxyphenyl)amino]-7-methoxybenzo[g]quinoline-3-carbonitrile as a yellow solid, mp 248–250° C. dec.

Workup

  1. temperaturethe mixture is heated at 80° C. for 2 hours
  2. temperaturethen cooled to room temperature
  3. custompartitioned between aqueous sodium bicarbonate and methylene chloride
  4. dry with materialThe organic layer is dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by column chromatography
  8. washeluting with 1:1 hexane/ethyl acetate

Sources & evidence

ORD record
ord-5761a33390cf4c2383139b40e1bb498a
Source dataset
uspto-grants-2006_09
Patent number
US07105531B2

Linked notes

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