Water → 5-[2-(5-chloro-2-fluoro-phenyl)-[1,8]naphthyridin-4-yl]-3-(1-methyl-1H-pyrazol-4-yl)-pyridin-2-ylamine

HRID 1914952Notes

Reaction equation

HRID 1914952 reaction equation
Br[C:2]1[C:3]([NH2:26])=[N:4][CH:5]=[C:6]([C:8]2[C:17]3[C:12](=[N:13][CH:14]=[CH:15][CH:16]=3)[N:11]=[C:10]([C:18]3[CH:23]=[C:22]([Cl:24])[CH:21]=[CH:20][C:19]=3[F:25])[CH:9]=2)[CH:7]=1.[CH3:27][N:28]1[CH:32]=[C:31](B2OC(C)(C)C(C)(C)O2)[CH:30]=[N:29]1.C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:24][C:22]1[CH:21]=[CH:20][C:19]([F:25])=[C:18]([C:10]2[CH:9]=[C:8]([C:6]3[CH:7]=[C:2]([C:31]4[CH:30]=[N:29][N:28]([CH3:27])[CH:32]=4)[C:3]([NH2:26])=[N:4][CH:5]=3)[C:17]3[C:12](=[N:13][CH:14]=[CH:15][CH:16]=3)[N:11]=2)[CH:23]=1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 67364390HCID 67364390, compound

Product 1

HCID 673631225-[2-(5-chloro-2-fluoro-phenyl)-[1,8]naphthyridin-4-yl]-3-(1-methyl-1H-pyrazol-4-yl)-pyridin-2-ylamine

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

A slurry of 297 mg (0.65 mmol) 3-bromo-5-[2-(5-chloro-2-fluoro-phenyl)-[1,8]naphthyridin-4-yl]-pyridin-2-ylamine, 270 mg (1.30 mmol) 1-methyl-1H-pyrazole-4-boronic acid pinacol ester and 270 mg (1.95 mmol) potassium carbonate in 3 ml DMF was flushed with nitrogen and then 75 mg (0.07 mmol) tetrakis(triphenylphosphine)-palladium were added. This mixture was heated for 30 minutes at a temperature of 130° C. in the microwave. Water was added to the reaction mixture and the resulting precipitate was filtered off and washed with water. The residue was chromatographed on a silica gel column with dichloromethane/methanol as eluent yielding 5-[2-(5-chloro-2-fluoro-phenyl)-[1,8]naphthyridin-4-yl]-3-(1-methyl-1H-pyrazol-4-yl)-pyridin-2-ylamine as yellow crystals; HPLC-MS: 1.57 min, [M+H] 431.

Workup

  1. filtrationthe resulting precipitate was filtered off
  2. washwashed with water
  3. customThe residue was chromatographed on a silica gel column with dichloromethane/methanol as eluent

Sources & evidence

ORD record
ord-63bd956747e947819f06a367669b2da8
Source dataset
uspto-grants-2013_12
Patent number
US08614226B2

Reaction notes

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