Triethylamine → [3-(4-{5-[2-(5-Chloro-2-fluoro-phenyl)-[1,8]naphthyridin-4-yl]-pyridin-3-yl}-pyrazol-1-yl)-propyl]-dimethyl-amine

HRID 1404301Notes

Reaction equation

HRID 1404301 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]([CH3:45])[CH2:28][CH2:29][CH2:30][N:31]1[CH:35]=[C:34](B2OC(C)(C)C(C)(C)O2)[CH:33]=[N:32]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>[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:3]=[C:2]([C:34]4[CH:33]=[N:32][N:31]([CH2:30][CH2:29][CH2:28][N:27]([CH3:26])[CH3:45])[CH:35]=4)[CH:7]=[N:6][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 8471TriethylamineHCID 6420914N,N-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-propanamineHCID 18407952Tripotassium phosphate trihydrateHCID 673643764-(5-Bromo-pyridin-3-yl)-2-(5-chloro-2-fluoro-phenyl)-[1,8]naphthyridine

Product 1

HCID 53345070[3-(4-{5-[2-(5-Chloro-2-fluoro-phenyl)-[1,8]naphthyridin-4-yl]-pyridin-3-yl}-pyrazol-1-yl)-propyl]-dimethyl-amine

Reagents, catalysts & solvents 2

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

Conditions

Temperature
85 °C

Procedure

A slurry of 500 mg (1.21 mmol) 4-(5-bromo-pyridin-3-yl)-2-(5-chloro-2-fluoro-phenyl)-[1,8]naphthyridine, 370 mg (1.33 mmol) dimethyl-{3-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazol-1-yl]-propyl}-amine and 512 mg (2.41 mmol) tri-potassium-phosphate-trihydrate in 5 ml 1,2-dimethoxyethane is heated to 85° C. under nitrogen. Then 42.3 mg (0.06 mmol) bis-(triphenylphosphine)-palladium(II)-chloride and 17 μl triethylamine were added. The reaction mixture was stirred for 2 hours at 85° C. The reaction mixture was partitioned between water and dichloromethane. The organic phase was dried over sodium sulfate and evaporated. The residue was crystallized from acetonitrile yielding [3-(4-{5-[2-(5-chloro-2-fluoro-phenyl)-[1,8]naphthyridin-4-yl]-pyridin-3-yl}-pyrazol-1-yl)-propyl]-dimethyl-amine as light grey crystals; HPLC-MS: 1.64 min, [M+H] 487.

Workup

  1. customThe reaction mixture was partitioned between water and dichloromethane
  2. dry with materialThe organic phase was dried over sodium sulfate
  3. customevaporated
  4. customThe residue was crystallized from acetonitrile

Sources & evidence

ORD record
ord-1db524988ce14f0089f6a75c79745747
Source dataset
uspto-grants-2014_12
Patent number
US08912216B2

Reaction notes

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