Potassium Carbonate → Tert-butyl 4-[2-chloro-6-[(4-cyano-2-pyridyl)amino]-4-pyridyl]piperidine-1-carboxylate

HRID 1057032Notes

Reaction equation

HRID 1057032 reaction equation
Cl[C:2]1[CH:7]=[C:6]([CH:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)[CH:5]=[C:4]([Cl:21])[N:3]=1.[NH2:22][C:23]1[CH:28]=[C:27]([C:29]#[N:30])[CH:26]=[CH:25][N:24]=1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+]>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]>[Cl:21][C:4]1[CH:5]=[C:6]([CH:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)[CH:7]=[C:2]([NH:22][C:23]2[CH:28]=[C:27]([C:29]#[N:30])[CH:26]=[CH:25][N:24]=2)[N:3]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 70155242-AminoisonicotinonitrileHCID 90015259Tert-butyl 4-(2,6-dichloropyridin-4-yl)piperidine-1-carboxylate

Product 1

HCID 90015343Tert-butyl 4-[2-chloro-6-[(4-cyano-2-pyridyl)amino]-4-pyridyl]piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
80 °C

Procedure

A round-bottomed flask was charged with tert-butyl 4-(2,6-dichloro-4-pyridyl)piperidine-1-carboxylate (3.64 g, 11.0 mmol), 2-amino-4-cyanopyridine (1.35 g, 11.0 mmol), tris(dibenzylideneacetone)dipalladium(0) (259 mg, 2.5 mol %), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (328 mg, 5 mol %) and potassium carbonate (2.13 g, 15.4 mmol). The flask was sealed with a septum and purged with nitrogen gas before injecting anhydrous 1,4-dioxane (22 mL, 0.5 M). The reaction mixture was stirred at 80° C. for 17 hr before cooling to rt and filtering through Celite, rinsing with CH2Cl2. After concentration, flash column chromatography (100:0-60:40 heptanes/EtOAc) afforded tert-butyl 4-[2-chloro-6-[(4-cyano-2-pyridyl)amino]-4-pyridyl]piperidine-1-carboxylate as a colorless film (1.745 g, 38%); 1H NMR (400 MHz, CDCl3) δ 8.40 (d, J=5.1 Hz, 1H), 7.94 (s, 1H), 7.42 (br s, 1H), 7.17 (s, 1H), 7.08 (d, J=5.1 Hz, 1H), 6.81 (s, 1H), 4.41-4.09 (m, 2H), 2.87-2.72 (m, 2H), 2.71-2.60 (m, 1H), 1.88-1.80 (m, 2H), 1.67-1.58 (m, 2H), 1.49 (s, 9H).

Workup

  1. customThe flask was sealed with a septum
  2. custompurged with nitrogen gas
  3. temperaturebefore cooling to rt
  4. filtrationfiltering through Celite
  5. washrinsing with CH2Cl2
  6. concentrationAfter concentration, flash column chromatography (100:0-60:40 heptanes/EtOAc)

Sources & evidence

ORD record
ord-2a7d3220db2d4ccf9ad7a37fc725ec14
Source dataset
uspto-grants-2016_07
Patent number
US09399636B2

Reaction notes

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