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3-Chloro-4-fluoroaniline → tert-Butyl 4-[(3-chloro-4-fluorophenyl)amino]-3-cyano-5,8-dihydrothieno[2,3-b:5,4-c']dipyridine-7(6H)-carboxylate

HRID 38541
Notes
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Reaction equation

HRID 38541 reaction equation
Cl[C:2]1[C:7]([C:8]#[N:9])=[CH:6][N:5]=[C:4]2[S:10][C:11]3[CH2:12][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:14][CH2:15][C:16]=3[C:3]=12.[Cl:24][C:25]1[CH:26]=[C:27]([CH:29]=[CH:30][C:31]=1[F:32])[NH2:28].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C(=O)([O-])[O-].[Cs+].[Cs+]>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].C1COCC1.CN(C=O)C>[Cl:24][C:25]1[CH:26]=[C:27]([NH:28][C:2]2[C:7]([C:8]#[N:9])=[CH:6][N:5]=[C:4]3[S:10][C:11]4[CH2:12][N:13]([C:17]([O:19][C:20]([CH3:21])([CH3:23])[CH3:22])=[O:18])[CH2:14][CH2:15][C:16]=4[C:3]=23)[CH:29]=[CH:30][C:31]=1[F:32]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 97083-Chloro-4-fluoroanilineHCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 58116935tert-Butyl 4-chloro-3-cyano-5,8-dihydrothieno[2,3-b:5,4-c']dipyridine-7(6H)-carboxylate

Product 1

HCID 58116801tert-Butyl 4-[(3-chloro-4-fluorophenyl)amino]-3-cyano-5,8-dihydrothieno[2,3-b:5,4-c']dipyridine-7(6H)-carboxylate
Yield 68%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of tert-butyl 4-chloro-3-cyano-5,8-dihydrothieno[2,3-b:5,4-c′]dipyridine-7(6H)-carboxylate from Example 53A (150 mg, 0.43 mmol) in a degassed mixture of DMF (1.5 mL) and THF (1.5 mL) were added 3-chloro-4-fluoroaniline (62 mg, 0.43 mmol), XPHOS (4.1 mg, 0.009 mmol), caesium carbonate (196 mg, 0.60 mmol) and tris(dibenzylideneacetone)dipalladium(0) (24 mg, 0.026 mmol). The mixture was heated to 90° C. for 1 h. The solvent was removed in vacuo, and the residue was purified by column chromatography on silica gel (eluent: DCM/MeOH 50:1) to yield 190 mg (70% purity, 68% yield) of the title compound, which was used in the next step without further purification.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue was purified by column chromatography on silica gel (eluent: DCM/MeOH 50:1)

Sources & evidence

ORD record
ord-86ef515523bc4511902653c08c8cb36c
Source dataset
uspto-grants-2013_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08524722B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes