Water → 2-(5-chloro-2-fluoro-phenyl)-4-{5-[1-(1-methyl-piperidin-4-yl)-1H-pyrazol-4-yl]-pyridin-3-yl}-[1,8]naphthyridine formate

HRID 1404298Notes

Reaction equation

HRID 1404298 reaction equation
Br[C:2]1[CH:3]=[C:4]([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:5]=[N:6][CH:7]=1.[CH3:26][N:27]1[CH2:32][CH2:31][CH:30]([N:33]2[CH:37]=[C:36](B3[O:42][C:41](C)(C)C(C)(C)O3)[CH:35]=[N:34]2)[CH2:29][CH2:28]1.[OH2:47]>>[CH:41]([OH:42])=[O:47].[Cl:24][C:22]1[CH:21]=[CH:20][C:19]([F:25])=[C:18]([C:10]2[CH:9]=[C:8]([C:4]3[CH:5]=[N:6][CH:7]=[C:2]([C:36]4[CH:35]=[N:34][N:33]([CH:30]5[CH2:31][CH2:32][N:27]([CH3:26])[CH2:28][CH2:29]5)[CH:37]=4)[CH:3]=3)[C:17]3[C:12](=[N:13][CH:14]=[CH:15][CH:16]=3)[N:11]=2)[CH:23]=1

Participants

4

Reactant 3

HCID 962WaterHCID 59231689(1-(1-Methylpiperidin-4-yl)-1H-pyrazol-4-yl)boronic acid pinacol esterHCID 673643764-(5-Bromo-pyridin-3-yl)-2-(5-chloro-2-fluoro-phenyl)-[1,8]naphthyridine

Product 1

HCID 710081402-(5-chloro-2-fluoro-phenyl)-4-{5-[1-(1-methyl-piperidin-4-yl)-1H-pyrazol-4-yl]-pyridin-3-yl}-[1,8]naphthyridine formate

Conditions

Temperature
80 °C

Procedure

To a solution of 59.7 mg (0.144 mmol) 4-(5-bromo-pyridin-3-yl)-2-(5-chloro-2-fluoro-phenyl)-[1,8]naphthyridine and 55.3 mg (0.190 mmol) 1-methyl-4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazol-1-yl]-piperidine 67.2 mg (0.316 mmol) tri-potassiumphosphate trihydrate were added. The mixture was heated to 80° C. under nitrogen. Then 5.5 mg (0.008 mmol) bis(triphenylphosphine)palladium(II)-chloride were added. The reaction mixture was stirred for 4 hours at 80° C. The reaction mixture was cooled to room temperature and water was added. The resulting precipitate was filtered off, washed with water and air-dried. The residue was purified by preparative HPLC yielding 2-(5-chloro-2-fluoro-phenyl)-4-{5-[1-(1-methyl-piperidin-4-yl)-1H-pyrazol-4-yl]-pyridin-3-yl}-[1,8]naphthyridine formate as colourless crystals; HPLC-MS: 1.29 min, [M+H] 292.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationThe resulting precipitate was filtered off
  3. washwashed with water
  4. customair-dried
  5. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-905cbc9317624418b300582c8b585915
Source dataset
uspto-grants-2014_12
Patent number
US08912216B2

Reaction notes

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