Triethylamine → HCID 67363289, compound

HRID 1914950Notes

Reaction equation

HRID 1914950 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.[C:26]([O:30][C:31]([N:33]1[CH2:38][CH2:37][CH:36]([N:39]2[CH:43]=[C:42](B3OC(C)(C)C(C)(C)O3)[CH:41]=[N:40]2)[CH2:35][CH2:34]1)=[O:32])([CH3:29])([CH3:28])[CH3:27].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>[C:26]([O:30][C:31]([N:33]1[CH2:34][CH2:35][CH:36]([N:39]2[CH:43]=[C:42]([C:2]3[CH:7]=[N:6][CH:5]=[C:4]([C:8]4[C:17]5[C:12](=[N:13][CH:14]=[CH:15][CH:16]=5)[N:11]=[C:10]([C:18]5[CH:23]=[C:22]([Cl:24])[CH:21]=[CH:20][C:19]=5[F:25])[CH:9]=4)[CH:3]=3)[CH:41]=[N:40]2)[CH2:37][CH2:38]1)=[O:32])([CH3:29])([CH3:27])[CH3:28]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 18407952Tripotassium phosphate trihydrateHCID 45480279tert-butyl 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylateHCID 673643764-(5-Bromo-pyridin-3-yl)-2-(5-chloro-2-fluoro-phenyl)-[1,8]naphthyridine

Product 1

HCID 67363289HCID 67363289, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
80 °C

Procedure

A slurry of 2.92 g (7.04 mmol) 4-(5-bromo-pyridin-3-yl)-2-(5-chloro-2-fluoro-phenyl)-[1,8]naphthyridine, 2.92 g (7.75 mmol) 4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazol-1-yl]-piperidine-1-carboxylic acid tert.butyl ester and 2.99 g (14.1 mmol) tri-potassium-phosphate-trihydrate in 30 ml 1,2-dimethoxyethane was heated to 80° C. under nitrogen. Then 247 mg (0.05 mmol) bis-(triphenylphosphine)-palladium(II)-chloride and 0.1 ml triethylamine were added. The reaction mixture was stirred for 16 hours at 80° C. The reaction mixture was partitioned between water and dichloromethane. The organic phase was dried over sodium sulfate and evaporated. The residue was chromatographed on a silica gel column with petrolether/ethylacetate as eluent yielding 4-(4-{5-[2-(5-chloro-2-fluoro-phenyl)-[1,8]naphthyridin-4-yl]-pyridin-3-yl}-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester as colourless crystals; HPLC-MS: 2.55 min, [M+H] 585.

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 chromatographed on a silica gel column with petrolether/ethylacetate as eluent

Sources & evidence

ORD record
ord-2d122b4097d247f5b4b8097486a7c482
Source dataset
uspto-grants-2013_12
Patent number
US08614226B2

Reaction notes

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