Potassium Carbonate → 6-Hydroxy-2-(3-(4-methylpiperazine-1-carbonyl)phenyl)quinoline-5-carbaldehyde

HRID 579452Notes

Reaction equation

HRID 579452 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.OC1C=C2C(C(C)=C([C:27]3[CH:43]=[CH:42][C:30]([C:31]([NH:33][CH2:34][CH2:35][N:36]4[CH2:41][CH2:40]OC[CH2:37]4)=[O:32])=[CH:29][CH:28]=3)C(=O)O2)=CC=1.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:27]=[CH:43][CH:42]=[C:30]([C:31]([N:33]4[CH2:34][CH2:35][N:36]([CH3:37])[CH2:41][CH2:40]4)=[O:32])[CH:29]=3)[CH:11]=[CH:10][C:9]=2[C:8]=1[CH:12]=[O:13]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 866834274-(7-Hydroxy-4-methyl-2-oxo-2H-chromen-3-yl)-N-(2-morpholinoethyl)benzamideHCID 866834282-Chloro-6-hydroxyquinoline-5-carbaldehyde

Product 1

HCID 866834306-Hydroxy-2-(3-(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), 3-(4-methylpiperazine-1-carbonyl)phenylboronic acid (6) (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 (d, 1H), 8.30 (dd, 1H), 8.27 (d, 1H), 8.24 (s, 1H), 8.23 (d, 1H), 7.61 (t, 1H), 7.49 (d, 1H), 7.47 (dd, 1H), 3.60, 3.40, 2.40 and 2.30 (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-cb178582fb3b48ce84e34b69d1953193
Source dataset
uspto-grants-2015_05
Patent number
US09040714B2

Reaction notes

Loading…