Dichloromethane → HCID 118566708, compound

HRID 1056803Notes

Reaction equation

HRID 1056803 reaction equation
[F:1][C:2]1([F:24])[CH2:7][CH2:6][CH:5]([CH2:8][NH:9][C:10]([C:12]2[C:13]3[CH:14]=[CH:15][C:16](Cl)=[N:17][C:18]=3[CH:19]=[CH:20][C:21]=2[Cl:22])=[O:11])[CH2:4][CH2:3]1.[CH3:25][N:26]1[CH2:31][CH:30]=[C:29](B2OC(C)(C)C(C)(C)O2)[CH2:28][CH2:27]1.C(=O)([O-])[O-].[Cs+].[Cs+].ClCCl>O1CCOCC1.O.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Fe]>[F:1][C:2]1([F:24])[CH2:7][CH2:6][CH:5]([CH2:8][NH:9][C:10]([C:12]2[C:13]3[CH:14]=[CH:15][C:16]([C:29]4[CH2:30][CH2:31][N:26]([CH3:25])[CH2:27][CH:28]=4)=[N:17][C:18]=3[CH:19]=[CH:20][C:21]=2[Cl:22])=[O:11])[CH2:4][CH2:3]1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 207733711-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridineHCID 1185559652,6-Dichloro-quinoline-5-carboxylic acid (4,4-difluorocyclohexylmethyl)-amide

Product 1

HCID 118566708HCID 118566708, compoundYield 47.5%

Reagents, catalysts & solvents 3

HCID 178477754HCID 178477754, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a suspension of 2,6-dichloro-quinoline-5-carboxylic acid (4,4-difluoro-cyclohexyl methyl)-amide (150 mg, 0.37 mmol, 1.00 eq) in 1,4-Dioxane (4.00 mL, 26.67 V) and water (0.50 mL, 3.33 V) was degassed with nitrogen for 15 minutes, then to this 1-methyl-1,2,3,6-tetrahydropyridine-4-boronic acid pinacol ester (101.25 mg, 0.44 mmol, 1.20 eq), cesium carbonate (362.17 mg, 1.10 mmol, 3.00 eq) and [1,1-bis(diphenyl phosphino)ferrocene]dichloropalladium (II), complex with dichloromethane (30.15 mg, 0.04 mmol, 0.10 eq) were added, then the reaction mixture was heated in pressure tube at 100° C. for 5 h. After completion of the reaction by TLC, the reaction mixture was cooled to room temperature, and filtered through celite, washed with ethyl acetate, and the filtrate was concentrated under reduced pressure to provide the crude compound, which was purified by column chromatography to afford the title compound (90 mg, 0.17 mmol, 47.5%) as a dark brown solid. m/z: 434.2 [M+H]+

Workup

  1. customwas degassed with nitrogen for 15 minutes
  2. customAfter completion of the reaction by TLC
  3. temperaturethe reaction mixture was cooled to room temperature
  4. filtrationfiltered through celite
  5. washwashed with ethyl acetate
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customto provide the crude compound, which
  8. customwas purified by column chromatography

Sources & evidence

ORD record
ord-8dc7039048d5406c813146ff45ff4225
Source dataset
uspto-grants-2016_07
Patent number
US09399623B2

Reaction notes

Loading…