Sodium Bicarbonate → HCID 68293201, compound

HRID 2171005Notes

Reaction equation

HRID 2171005 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].[F:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[C:33]1[CH:34]=[C:35](B(O)O)[C:36]2[C:37]([N:42]=1)=[N:38][CH:39]=[CH:40][N:41]=2.C(=O)([O-])O.[Na+]>CN(C=O)C.O.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:35]4[C:36]5[C:37](=[N:38][CH:39]=[CH:40][N:41]=5)[N:42]=[C:33]([C:28]5[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=5[F:26])[CH:34]=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 66653094HCID 66653094, compoundHCID 68292755HCID 68292755, compound

Product 1

HCID 68293201HCID 68293201, compound

Reagents, catalysts & solvents 3

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 962WaterSolvent2×HCID 21962138N,N-Dimethylformamide--water (1/1)Solvent

Conditions

Temperature
80 °C

Procedure

A suspension of 296 mg (0.73 mmol) 4-[4-(5-bromo-pyridin-3-yl)-pyrazol-1-yl]-piperidine-1-carboxylic acid tert-butyl-ester, 215 mg (0.80 mmol) [6-(2-fluorophenyl)pyrido[2,3-b]pyrazin-8-yl]-boronic acid and 10 mg (0.015 mmol) bis-(triphenylphosphine)-palladium(II)-chloride in 1.5 ml DMF water was heated to 80° C. under nitrogen. Then a solution of 73 mg (0.87 mmol) sodium hydrogen carbonate in 0.75 ml water was added. The reaction mixture was stirred for 20 hours at 80° C. The reaction mixture was cooled to room temperature. Water was added, the resulting precipitate was filtered off, washed with water and dried under vacuum. The residue was chromatographed on a silica gel column with dichloromethane/methanol as eluent yielding 4-(4-{5-[6-(2-fluoro-phenyl)-pyrido[2,3-b]pyrazin-8-yl]-pyridin-3-yl}-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester as off-white solid crystals; HPLC-MS (A): 2.37 min, [M+H] 552.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationthe resulting precipitate was filtered off
  3. washwashed with water
  4. customdried under vacuum
  5. customThe residue was chromatographed on a silica gel column with dichloromethane/methanol as eluent

Sources & evidence

ORD record
ord-06070335a0764a318140564d5352a4c4
Source dataset
uspto-grants-2015_06
Patent number
US09051318B2

Reaction notes

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