Potassium Phosphate, Tribasic → 7-Dimethylamino-3-(2-methyl-3-{1-methyl-5-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-phenyl)-1H-quinolin-4-one

HRID 2069772Notes

Reaction equation

HRID 2069772 reaction equation
[CH3:1][N:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:5]=[C:4]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]([N:26]3[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)=[O:25])=[CH:20][N:19]=2)[C:3]1=[O:32].Br[C:34]1[C:35]([CH3:54])=[C:36]([C:40]2[C:49](=[O:50])[C:48]3[C:43](=[CH:44][C:45]([N:51]([CH3:53])[CH3:52])=[CH:46][CH:47]=3)[NH:42][CH:41]=2)[CH:37]=[CH:38][CH:39]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>>[CH3:53][N:51]([CH3:52])[C:45]1[CH:44]=[C:43]2[C:48]([C:49](=[O:50])[C:40]([C:36]3[CH:37]=[CH:38][CH:39]=[C:34]([C:6]4[CH:5]=[C:4]([NH:17][C:18]5[CH:23]=[CH:22][C:21]([C:24]([N:26]6[CH2:31][CH2:30][O:29][CH2:28][CH2:27]6)=[O:25])=[CH:20][N:19]=5)[C:3](=[O:32])[N:2]([CH3:1])[CH:7]=4)[C:35]=3[CH3:54])=[CH:41][NH:42]2)=[CH:47][CH:46]=1

Participants

4

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 574241463-(3-Bromo-2-methyl-phenyl)-7-dimethylamino-1H-quinolin-4-oneHCID 592164661-Methyl-3-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyridin-2-one

Product 1

HCID 441826507-Dimethylamino-3-(2-methyl-3-{1-methyl-5-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-phenyl)-1H-quinolin-4-oneYield 38.7%

Conditions

Temperature
100 °C

Procedure

To Methyl-3-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyridin-2-one (27 mg, 0.062 mmol), 3-(3-Bromo-2-methyl-phenyl)-7-dimethylamino-1H-quinolin-4-one (22 mg, 0.062 mmol), potassium phosphate (26 mg, 0.12 mmol), 2-(dicyclohexylphoshphino)-2′,4′,6′-tri-i-propyl-1,1′-biphenyl (1.7 mg, 0.0036 mmol), and bis(dibenzylidineacetone)palladium(0) (1.0 mg, 0.0018 mmol) was added 4 mL of degassed 1:3 water/n-butanol. The headspace of the vessel was evacuated and backfilled with argon 4 times. This was heated at 100° C. for 1 hour. This was partitioned between ethyl acetate and water. The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, concentrated in vacuo, and purified by preparative TLC (5% methanol/dichloromethane) to yield 7-Dimethylamino-3-(2-methyl-3-{1-methyl-5-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-phenyl)-1H-quinolin-4-one (14 mg, 0.024 mmol). MS (ESI) 591.1 (M+H)+.

Workup

  1. customof degassed 1:3 water/n-butanol
  2. customThe headspace of the vessel was evacuated
  3. customThis was partitioned between ethyl acetate and water
  4. washThe ethyl acetate layer was washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. custompurified by preparative TLC (5% methanol/dichloromethane)

Sources & evidence

ORD record
ord-bf35b615040645e3bc61d08f5a5ea903
Source dataset
uspto-grants-2012_10
Patent number
US08299077B2

Reaction notes

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