Potassium Carbonate → 6-Hydroxy-2-(4-(4-methylpiperazine-1-carbonyl)phenyl)quinoline-5-carbaldehyde

HRID 579451Notes

Reaction equation

HRID 579451 reaction equation
Cl[C:2]1[CH:11]=[CH:10][C:9]2[C:8]([CH:12]=[O:13])=[C:7]([OH:14])[CH:6]=[CH:5][C:4]=2[N:3]=1.C(C1C(O)=CC=C2C=1OC(=O)C([C:28]1[CH:44]=[CH:43][C:31]([C:32]([NH:34][CH2:35][CH2:36][N:37]3[CH2:42][CH2:41]OC[CH2:38]3)=[O:33])=[CH:30][CH:29]=1)=C2C)=O.C([O-])([O-])=O.[K+].[K+]>CC(O)C.O>[OH:14][C:7]1[CH:6]=[CH:5][C:4]2[N:3]=[C:2]([C:28]3[CH:29]=[CH:30][C:31]([C:32]([N:34]4[CH2:35][CH2:36][N:37]([CH3:38])[CH2:42][CH2:41]4)=[O:33])=[CH:43][CH:44]=3)[CH:11]=[CH:10][C:9]=2[C:8]=1[CH:12]=[O:13]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 54575078IRE1|A kinase-IN-9HCID 866834282-Chloro-6-hydroxyquinoline-5-carbaldehyde

Product 1

HCID 545759296-Hydroxy-2-(4-(4-methylpiperazine-1-carbonyl)phenyl)quinoline-5-carbaldehyde

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3776IsopropanolSolvent

Procedure

A mixture of 2-chloro-6-hydroxyquinolin-5-carbaldehyde (3) (104 mg, 0.5 mmol), 4-(4-methylpiperazine-1-carbonyl)phenylboronic acid (4) (198 mg, 0.7 mmol) and K2CO3 (174 mg, 1.25 mmol) in a mixture of i-PrOH and water (6 mL 10:1) was purged with Argon for five minutes in a microwave vessel. A tablet of PdOAc2(Sphos)4 (Aldrich, Cat. No. 694088) was added under an Argon atmosphere then the vessel was sealed and irradiated for 45 min at 165° C. Upon cooling, the reaction mixture was filtered through a silica plug using MeOH. The solution was evaporated and purified by Flash chromatography using 0-5% MeOH in CH2Cl2. The product was recrystallized from CH2Cl2/hexanes to afford the title compound. MS (ESI): 376 (M+H)+. 1H NMR (δ, DMSO (2.5 ppm)): 10.74 (s, 1H), 9.44 8.25, 7.21 and 7.49 (4d, 4×1H), 8.29 and 7.54 (2d, 2×2H), 3.64, 3.38, 2.41 and 2.33 (4 broad s, 4×2H), 2.23 (s, 3H).

Workup

  1. customwas purged with Argon for five minutes in a microwave vessel
  2. addition694088) was added under an Argon atmosphere
  3. customthe vessel was sealed
  4. customirradiated for 45 min at 165° C
  5. temperatureUpon cooling
  6. filtrationthe reaction mixture was filtered through a silica plug
  7. customThe solution was evaporated
  8. custompurified by Flash chromatography
  9. customThe product was recrystallized from CH2Cl2/hexanes

Sources & evidence

ORD record
ord-5ae7c53812924dea8859f4926f0e92de
Source dataset
uspto-grants-2015_05
Patent number
US09040714B2

Reaction notes

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