Triethylamine → 2-(5-chloro-2-fluoro-phenyl)-4-{6-[1-(2-pyrrolidin-1-yl-ethyl)-1H-pyrazol-4-yl]-pyrazin-2-yl}-[1,8]naphthyridine

HRID 1404313Notes

Reaction equation

HRID 1404313 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:25])=[C:6]([C:8]2[CH:17]=[C:16]([C:18]3[CH:23]=[N:22][CH:21]=[C:20](Cl)[N:19]=3)[C:15]3[C:10](=[N:11][CH:12]=[CH:13][CH:14]=3)[N:9]=2)[CH:7]=1.[N:26]1([CH2:31][CH2:32][N:33]2[CH:37]=[C:36](B3OC(C)(C)C(C)(C)O3)[CH:35]=[N:34]2)[CH2:30][CH2:29][CH2:28][CH2:27]1.O.O.O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(N(CC)CC)C>COCCOC.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:25])=[C:6]([C:8]2[CH:17]=[C:16]([C:18]3[CH:23]=[N:22][CH:21]=[C:20]([C:36]4[CH:35]=[N:34][N:33]([CH2:32][CH2:31][N:26]5[CH2:30][CH2:29][CH2:28][CH2:27]5)[CH:37]=4)[N:19]=3)[C:15]3[C:10](=[N:11][CH:12]=[CH:13][CH:14]=3)[N:9]=2)[CH:7]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 18407952Tripotassium phosphate trihydrateHCID 588858611-(2-(pyrrolidin-1-yl)ethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 86673735HCID 86673735, compound

Product 1

HCID 673655352-(5-chloro-2-fluoro-phenyl)-4-{6-[1-(2-pyrrolidin-1-yl-ethyl)-1H-pyrazol-4-yl]-pyrazin-2-yl}-[1,8]naphthyridine

Reagents, catalysts & solvents 3

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

A slurry of 115 mg (0.31 mmol) 2-(5-chloro-2-fluoro-phenyl)-4-(6-chloro-pyrazin-2-yl)-[1,8]naphthyridine, 99.3 mg (0.34 mmol) 1-(2-pyrrolidin-1-yl-ethyl)-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole and 165 mg (0.62 mmol) tri-potassium-phosphate-trihydrate in 1 ml 1,2-dimethoxyethane was heated to 80° C. under nitrogen. Then 4.3 mg (0.006 mmol) bis-(triphenylphosphine)-palladium(II)-chloride and a drop of triethylamine were added. The reaction mixture was stirred for 18 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 chromatographed on a silica gel column with dichloromethane/methanol as eluent to yield 2-(5-chloro-2-fluoro-phenyl)-4-{6-[1-(2-pyrrolidin-1-yl-ethyl)-1H-pyrazol-4-yl]-pyrazin-2-yl}-[1,8]naphthyridine as grey crystals; HPLC-MS: 1.52 min, [M+H] 500.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationThe resulting precipitate was filtered off
  3. washwashed with water
  4. customchromatographed on a silica gel column with dichloromethane/methanol as eluent

Sources & evidence

ORD record
ord-66a11ce6441a4f87bdc75a7aa27a63c6
Source dataset
uspto-grants-2014_12
Patent number
US08912216B2

Reaction notes

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