Sodium Bicarbonate → HCID 67363289, compound

HRID 1914943Notes

Reaction equation

HRID 1914943 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:18]=[C:17]([C:19]3[CH:20]=[N:21][CH:22]=[C:23](Br)[CH:24]=3)[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:26][C:27]1[CH:28]=[CH:29][C:30]([F:46])=[C:31]([C:33]2[CH:42]=[C:41](B(O)O)[C:40]3[C:35](=[N:36][CH:37]=[CH:38][CH:39]=3)[N:34]=2)[CH:32]=1.C(=O)(O)[O-].[Na+]>CN(C=O)C.O.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:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:18]=[C:17]([C:19]3[CH:20]=[N:21][CH:22]=[C:23]([C:41]4[C:40]5[C:35](=[N:36][CH:37]=[CH:38][CH:39]=5)[N:34]=[C:33]([C:31]5[CH:32]=[C:27]([Cl:26])[CH:28]=[CH:29][C:30]=5[F:46])[CH:42]=4)[CH:24]=3)[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 53344730HCID 53344730, compoundHCID 66653094HCID 66653094, compound

Product 1

HCID 67363289HCID 67363289, compound

Reagents, catalysts & solvents 3

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A slurry of 204 mg (0.50 mmol) 4-[4-(5-bromo-pyridin-3-yl)-pyrazol-1-yl]-piperidine-1-carboxylic acid tert-butyl-ester, 167 mg (0.55 mmol) 2-(5-chloro-2-fluoro-phenyl)-[1,8]naphthyridine-4-boronic acid and 50.4 mg (0.6 mmol) sodium bicarbonate in 2 ml DMF and 0.5 ml water were heated to 80° C. under nitrogen. Then 7.0 mg (0.01 mmol) bis-(triphenylphosphine)-palladium(II)-chloride were added. The reaction mixture was stirred for 40 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-78ba946b6e6c4134b4b27023d5615918
Source dataset
uspto-grants-2013_12
Patent number
US08614226B2

Reaction notes

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