Acetonitrile → 2-[2-(3-pyridyl)thiazol-5-yl]-6,7-dihydro-5H-quinolin-8-one

HRID 2279268Notes

Reaction equation

HRID 2279268 reaction equation
C(#N)C.C([O-])([O-])=O.[Na+].[Na+].[N:10]1[CH:15]=[CH:14][CH:13]=[C:12]([C:16]2[S:17][C:18](B3OC(C)(C)C(C)(C)O3)=[CH:19][N:20]=2)[CH:11]=1.Cl[C:31]1[CH:40]=[CH:39][C:38]2[CH2:37][CH2:36][CH2:35][C:34](=[O:41])[C:33]=2[N:32]=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[N:10]1[CH:15]=[CH:14][CH:13]=[C:12]([C:16]2[S:17][C:18]([C:31]3[CH:40]=[CH:39][C:38]4[CH2:37][CH2:36][CH2:35][C:34](=[O:41])[C:33]=4[N:32]=3)=[CH:19][N:20]=2)[CH:11]=1

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 10340Sodium CarbonateHCID 146801122-Chloro-5,6,7,8-tetrahydroquinolin-8-oneHCID 457865052-(Pyridin-3-yl)thiazole-5-boronic acid pinacol ester

Product 1

HCID 1180732922-[2-(3-pyridyl)thiazol-5-yl]-6,7-dihydro-5H-quinolin-8-oneYield 21%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×

Conditions

Temperature
80 °C

Procedure

A screw cap vial was charged with acetonitrile (8 mL), water (2.5 mL) and Na2CO3 (1.41 g, 13.0 mmol, 4.7 equiv.) and degassed by bubbling nitrogen through for 10 min. Then 2-(3-pyridyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiazole (800 mg, 2.78 mmol, 1.0 equiv.), 2-chloro-6,7-dihydro-5H-quinolin-8-one (807 mg, 4.44 mmol, 1.6 equiv.) and Pd(PPh3)4 (161 mg, 0.139 mmol, 0.05 equiv.) were added and the mixture was heated to 80° C. for 18 hours. Water was added to the mixture, the aqueous phase was extracted twice with ethyl acetate, the combined organic phase were washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluant gradient: Heptane/ethyl acetate 1:0 to 0:1) to afford the title compound (180 mg, 0.58 mmol, 21%) as brown crystals. LCMS (+ve); 0.76 min, 308 (M+1)

Workup

  1. customA screw cap vial
  2. customdegassed
  3. customby bubbling nitrogen through for 10 min
  4. extractionthe aqueous phase was extracted twice with ethyl acetate
  5. washthe combined organic phase were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography on silica gel (eluant gradient: Heptane/ethyl acetate 1:0 to 0:1)

Sources & evidence

ORD record
ord-f82f7ce3733642238138e20539e504c1
Source dataset
uspto-grants-2015_09
Patent number
US09133218B2

Reaction notes

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