Potassium Phosphate, Tribasic → HCID 10344894, compound

HRID 1611546Notes

Reaction equation

HRID 1611546 reaction equation
Cl[C:2]1[C:7]([C:8]#[N:9])=[CH:6][N:5]=[C:4]2[CH:10]=[C:11](/[CH:13]=[CH:14]/[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[S:12][C:3]=12.[Cl:22][C:23]1[CH:29]=[C:28]([Cl:30])[C:27]([O:31][CH3:32])=[CH:26][C:24]=1[NH2:25].P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1>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]>[C:8]([C:7]1[C:2]([NH:25][C:24]2[CH:26]=[C:27]([O:31][CH3:32])[C:28]([Cl:30])=[CH:29][C:23]=2[Cl:22])=[C:3]2[S:12][C:11](/[CH:13]=[CH:14]/[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[CH:10][C:4]2=[N:5][CH:6]=1)#[N:9]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 14766362,4-Dichloro-5-methoxyanilineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 86593499HCID 86593499, compound

Product 1

HCID 10344894HCID 10344894, compoundYield 54.7%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
90 °C

Procedure

A mixture of tert-butyl (2E)-3-(7-chloro-6-cyanothieno[3,2-b]pyridin-2-yl)prop-2-enoate (1.29 g, 3.74 mmol), 2,4-dichloro-5-methoxyaniline (862 mg, 4.49 mmol), Tris(dibenzylideneacetone)-dipalladium(0) (343 mg, 0.37 mmol), potassium phosphate (1.29 g, 5.61 mmol) and 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (456 mg, 1.16 mmol) in 36 mL of ethylene glycol dimethyl ether is heated at 90° C. for 3 hours. The reaction mixture is cooled to room temperature and partitioned between water and ethyl acetate. The aqueous layer is extracted with additional ethyl acetate and the organic layers are combined, dried over sodium sulfate, filtered and concentrated in vacuo. The residue is purified by flash column chromatography eluting with a gradient of hexane to 40% ethyl acetate in hexane to provide 974 mg of tert-butyl (2E)-3-{6-cyano-7-[(2,4-dichloro-5-methoxyphenyl)amino]thieno[3,2-b]pyridin-2-yl}prop-2-enoate as a light tan solid, mp 224° C. dec; 1H NMR (DMSO-d6) δ 1.48 (s, 9H), 3.85 (s, 3H), 6.26 (d, J=16 Hz, 1H), 7.37 (s, 1H), 7.75 (d, J=16 Hz, 1H), 7.78 (s, 1H), 7.91 (s, 1H), 8.62 (s, 1H), 9.80 (s, 1H); MS 476.0, 478.0 (M+H)+.

Workup

  1. temperatureThe reaction mixture is cooled to room temperature
  2. custompartitioned between water and ethyl acetate
  3. extractionThe aqueous layer is extracted with additional ethyl acetate
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue is purified by flash column chromatography
  8. washeluting with a gradient of hexane to 40% ethyl acetate in hexane

Sources & evidence

ORD record
ord-dd19b16764f449a9bece6f6e2dc9bdf0
Source dataset
uspto-grants-2006_01
Patent number
US06987116B2

Reaction notes

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