1-Bromo-3-chlorobenzene → 1-((2S,4R)-4-((3-chlorophenyl)amino)-2-methyl-6-(6-(morpholine-4-carbonyl)pyridin-3-yl)-3,4-dihydroquinolin-1(2H)-yl)ethanone

HRID 882302Notes

Reaction equation

HRID 882302 reaction equation
[NH2:1][C@H:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]3[CH:13]=[N:14][C:15]([C:18]([N:20]4[CH2:25][CH2:24][O:23][CH2:22][CH2:21]4)=[O:19])=[CH:16][CH:17]=3)[CH:10]=2)[N:5]([C:26](=[O:28])[CH3:27])[C@@H:4]([CH3:29])[CH2:3]1.Br[C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([Cl:37])[CH:32]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(N(C)C)=CC=CC=2)CCCCC1.CC(C)([O-])C.[Na+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:37][C:33]1[CH:32]=[C:31]([NH:1][C@H:2]2[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([C:12]4[CH:13]=[N:14][C:15]([C:18]([N:20]5[CH2:25][CH2:24][O:23][CH2:22][CH2:21]5)=[O:19])=[CH:16][CH:17]=4)[CH:10]=3)[N:5]([C:26](=[O:28])[CH3:27])[C@@H:4]([CH3:29])[CH2:3]2)[CH:36]=[CH:35][CH:34]=1

Participants

7

Reactant 4

HCID 79281-Bromo-3-chlorobenzeneHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 23676156Sodium t-butoxideHCID 867094251-((2S,4R)-4-amino-2-methyl-6-(6-(morpholine-4-carbonyl)pyridin-3-yl)-3,4-dihydroquinolin-1(2H)-yl)ethanone

Product 1

HCID 714680291-((2S,4R)-4-((3-chlorophenyl)amino)-2-methyl-6-(6-(morpholine-4-carbonyl)pyridin-3-yl)-3,4-dihydroquinolin-1(2H)-yl)ethanoneYield 45%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

1-((2S,4R)-4-amino-2-methyl-6-(6-(morpholine-4-carbonyl)pyridin-3-yl)-3,4-dihydroquinolin-1(2H)-yl)ethanone (for a preparation, see Intermediate 56) (100 mg, 0.254 mmol), 1-bromo-3-chlorobenzene (0.060 mL, 0.507 mmol), 2′-(dicyclohexylphosphino)-N,N-dimethyl-[1,1′-biphenyl]-2-amine (20.0 mg, 0.051 mmol), tris(dibenzylideneacetone)dipalladium(0) (23.3 mg, 0.025 mmol) and sodium tert-butoxide (34.1 mg, 0.355 mmol) were combined in 1,4-dioxane (2.5 mL). The mixture was degassed over a period of 15 mins before being heated under microwave irradiation to 120° C. for 25 mins. The mixture was partitioned between water (50 mL) and DCM (3×50 mL). The organic layers were combined, dried by passing through a hydrophobic frit and concentrated in vacuo. The resulting residue was purified by MDAP (HpH) to give 1-((2S,4R)-4-((3-chlorophenyl)amino)-2-methyl-6-(6-(morpholine-4-carbonyl)pyridin-3-yl)-3,4-dihydroquinolin-1(2H)-yl)ethanone (58 mg, 0.115 mmol, 45% yield).

Workup

  1. customThe mixture was degassed over a period of 15 mins
  2. customThe mixture was partitioned between water (50 mL) and DCM (3×50 mL)
  3. customdried
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue was purified by MDAP (HpH)

Sources & evidence

ORD record
ord-fad47f83f52249eb86017a63f0c8ba4c
Source dataset
uspto-grants-2015_03
Patent number
US08993554B2

Reaction notes

Loading…