Cesium carbonate → 5-(5-(4-Methoxyphenyl)-4-(1-methylpiperidin-4-ylamino)pyridin-2-ylamino)pyrazine-2-carbonitrile

HRID 384688Notes

Reaction equation

HRID 384688 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([NH:8][CH:9]2[CH2:14][CH2:13][N:12]([C:15](OC(C)(C)C)=O)[CH2:11][CH2:10]2)[C:5]([C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=2)=[CH:4][N:3]=1.Br[C:31]1[N:32]=[CH:33][C:34]([C:37]#[N:38])=[N:35][CH:36]=1.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.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].COCCOC>[CH3:29][O:28][C:25]1[CH:26]=[CH:27][C:22]([C:5]2[C:6]([NH:8][CH:9]3[CH2:14][CH2:13][N:12]([CH3:15])[CH2:11][CH2:10]3)=[CH:7][C:2]([NH:1][C:31]3[N:32]=[CH:33][C:34]([C:37]#[N:38])=[N:35][CH:36]=3)=[N:3][CH:4]=2)=[CH:23][CH:24]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 378187222-Bromo-5-cyanopyrazineHCID 59613346Tert-butyl 4-(2-amino-5-(4-methoxyphenyl)pyridin-4-ylamino)piperidine-1-carboxylate

Product 1

HCID 596134065-(5-(4-Methoxyphenyl)-4-(1-methylpiperidin-4-ylamino)pyridin-2-ylamino)pyrazine-2-carbonitrileYield 20%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

Dry DME (402 μL) was added to a mixture of tert-butyl 4-(2-amino-5-(4-methoxyphenyl)pyridin-4-ylamino)piperidine-1-carboxylate (16 mg, 0.040 mmol), 5-bromopyrazine-2-carbonitrile (7.39 mg, 0.040 mmol), xantphos (1.859 mg, 3.21 μmol), tris(dibenzylideneacetone)dipalladium(0) (1.471 mg, 1.606 μmol), and cesium carbonate (26.2 mg, 0.080 mmol) in a nitrogen purged, sealed microwave vial. Nitrogen gas was bubbled through the mixture for 5 min. The reaction mixture was heated for 1 hr at 100° C. by microwave irradiation. Upon cooling the mixture was diluted with MeOH and purified by ion exchange on Isolute SCX II acidic resin (5 g), eluting with MeOH. The eluent was concentrated and further purified by preparative thin layer chromatography, eluting with 7% MeOH, 1% NH3, 92% DCM, to give 5-(5-(4-methoxyphenyl)-4-(1-methylpiperidin-4-ylamino)pyridin-2-ylamino)pyrazine-2-carbonitrile (4 mg, 7.97 μmol, 20% yield) as a light yellow powder.

Workup

  1. custompurged
  2. customsealed microwave vial
  3. customNitrogen gas was bubbled through the mixture for 5 min
  4. temperatureUpon cooling the mixture
  5. additionwas diluted with MeOH
  6. custompurified by ion exchange on Isolute SCX II acidic resin (5 g)
  7. washeluting with MeOH
  8. concentrationThe eluent was concentrated
  9. customfurther purified by preparative thin layer chromatography
  10. washeluting with 7% MeOH, 1% NH3, 92% DCM

Sources & evidence

ORD record
ord-7d949b9440744e959f26476f7d2f7448
Source dataset
uspto-grants-2013_02
Patent number
US08367658B2

Reaction notes

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