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3-Aminoquinoline → 2-(5-Cyano-3-fluoro-6-(quinolin-3-ylamino)pyridin-2-ylamino)-4,4,4-trifluorobutanamide

HRID 84926
Notes
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Reaction equation

HRID 84926 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][CH:9]([CH2:13][C:14]([F:17])([F:16])[F:15])[C:10]([NH2:12])=[O:11])[C:5]([F:18])=[CH:4][C:3]=1[C:19]#[N:20].[NH2:21][C:22]1[CH:23]=[N:24][C:25]2[C:30]([CH:31]=1)=[CH:29][CH:28]=[CH:27][CH:26]=2.O.O.O.[O-]C1C=CC=CC=1.[Na+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.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:19]([C:3]1[CH:4]=[C:5]([F:18])[C:6]([NH:8][CH:9]([CH2:13][C:14]([F:17])([F:16])[F:15])[C:10]([NH2:12])=[O:11])=[N:7][C:2]=1[NH:21][C:22]1[CH:23]=[N:24][C:25]2[C:30]([CH:31]=1)=[CH:29][CH:28]=[CH:27][CH:26]=2)#[N:20]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 113753-AminoquinolineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23681143Sodium Phenoxide TrihydrateHCID 866661702-(6-Chloro-5-cyano-3-fluoropyridin-2-ylamino)-4,4,4-trifluorobutanamide

Product 1

HCID 675082802-(5-Cyano-3-fluoro-6-(quinolin-3-ylamino)pyridin-2-ylamino)-4,4,4-trifluorobutanamide
Yield 122.9%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of the crude 2-(6-chloro-5-cyano-3-fluoropyridin-2-ylamino)-4,4,4-trifluorobutanamide (109 mg, 0.350 mmol), 3-aminoquinoline (52 mg, 0.361 mmol), sodium phenoxide trihydrate (85 mg, 0.500 mmol), xantphos (30 mg, 0.051 mmol) and Pd2 dba3 (20 mg, 0.021 mmol) in dioxane (2 mL) was degassed with Ar, then was stirred at 105 C for 3 h. Water and EtOAc were added. The organic phase was washed with aq. 1N NaOH, dried over Na2SO4, concentrated in vacuo to give crude 2-(5-cyano-3-fluoro-6-(quinolin-3-ylamino)pyridin-2-ylamino)-4,4,4-trifluorobutanamide (180 mg).

Workup

  1. customwas degassed with Ar
  2. additionWater and EtOAc were added
  3. washThe organic phase was washed with aq. 1N NaOH
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-bfd2582fd15d401c9fb9dde2be49e3fc
Source dataset
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08846928B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes