2-Chloropyridine → HCID 25096016, compound

HRID 2192965Notes

Reaction equation

HRID 2192965 reaction equation
ClC1C=CC=CN=1.[NH:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]1=[O:14].ClC1N=CC=C2C=1[C:18]1[CH:38]=[N:37][CH:36]=[CH:35][C:19]=1[C:20]([NH:26][C@@H:27]([C:31]([F:34])([F:33])[F:32])[CH:28]([CH3:30])[CH3:29])=[N:21]2.[OH-].[K+]>O1CCOCC1.O.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].CCOC(C)=O>[CH3:29][CH:28]([CH3:30])[C@@H:27]([NH:26][C:20]1[C:19]2[CH:18]=[CH:38][N:37]=[CH:36][C:35]=2[C:10]2[C:9](=[O:14])[NH:8][CH:13]=[CH:12][C:11]=2[N:21]=1)[C:31]([F:34])([F:32])[F:33]

Participants

9

Reactant 4

HCID 79772-ChloropyridineHCID 88712-PyridoneHCID 14797Potassium HydroxideHCID 59375537HCID 59375537, compound

Product 1

HCID 25096016HCID 25096016, compound

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

The 2-chloro pyridine was converted the pyridone following the procedure of J. Am. Chem. Soc. 2006, 128, 1094-10695. To a solution of 1-chloro-N-[(1R)-2-methyl-1-(trifluoromethyl)propyl]pyrido[4,3-c]-1,6-naphthyridin-6-amine (1100 mg, 3.10 mmol) in dioxane (10 mL) and water (10 mL) was added KOH (696 mg, 12.4 mmol), 1-[2′-(di-tert-butylphosphino)-2,6-diisopropylbiphenyl-4-yl]ethyl (263 mg, 0.62 mmol) and Pd2 (dba)3 (284 mg, 0.31 mmol). The stirring solution was heated to 100° C. overnight. The reaction mixture was cooled and worked up with EtOAc and water. The organic layers were separated, dried with MgSO4, filtered, and concentrated by rotary evaporation. The oily residue was purified by silica gel column chromatography CH2Cl2 to MeOH 30% provided the 6-{[(1R)-2-methyl-1-(trifluoromethyl)propyl]amino}pyrido[4,3-c]-1,6-naphthyridin-1(2H)-one. 1H NMR (600 MHz, CD3OD) δ 11.30 (s, 1H), 9.05 (d, 1H), 8.95 (d, 1H), 7.62 (d, 1H), 6.80 (d, 1H), 5.48 (m, 1H), 2.40 (m, 1H), 1.17 (d, 3H), 1.10 (d, 3H). LRMS (ESI) calc'd for (C16H16F3N4O) [M+H]+, 337.1; found 337.1.

Workup

  1. temperatureThe reaction mixture was cooled
  2. customThe organic layers were separated
  3. dry with materialdried with MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated by rotary evaporation
  6. customThe oily residue was purified by silica gel column chromatography CH2Cl2 to MeOH 30%

Sources & evidence

ORD record
ord-c6268bd12df54c55916bffd137f22ae3
Source dataset
uspto-grants-2012_12
Patent number
US08329722B2

Reaction notes

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