Potassium Carbonate → N-(3-(5-Chloro-2-((3-Hydroxy-4-Morpholinophenyl)Amino)Pyrimidin-4-Yl)Phenyl)Acrylamide

HRID 929691Notes

Reaction equation

HRID 929691 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[C:10]([NH:14][C:15](=[O:18])[CH:16]=[CH2:17])[CH:11]=[CH:12][CH:13]=2)[C:5]([Cl:19])=[CH:4][N:3]=1.[NH2:20][C:21]1[CH:22]=[CH:23][C:24]([N:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)=[C:25]([OH:27])[CH:26]=1.C(=O)([O-])[O-].[K+].[K+]>CC(O)(C)C.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].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>[Cl:19][C:5]1[C:6]([C:8]2[CH:9]=[C:10]([NH:14][C:15](=[O:18])[CH:16]=[CH2:17])[CH:11]=[CH:12][CH:13]=2)=[N:7][C:2]([NH:20][C:21]2[CH:22]=[CH:23][C:24]([N:28]3[CH2:29][CH2:30][O:31][CH2:32][CH2:33]3)=[C:25]([OH:27])[CH:26]=2)=[N:3][CH:4]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 539059685-Amino-2-morpholinophenolHCID 71469246N-(3-(2,5-dichloropyrimidin-4-yl)phenyl)acrylamide

Product 1

HCID 73438564N-(3-(5-Chloro-2-((3-Hydroxy-4-Morpholinophenyl)Amino)Pyrimidin-4-Yl)Phenyl)AcrylamideYield 51.6%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6386tert-ButanolSolvent

Conditions

Temperature
140 °C

Procedure

N-(3-(2,5-dichloropyrimidin-4-yl)phenyl)acrylamide (151 mg, 0.515 mmol), 5-amino-2-morpholinophenol (100 mg, 0.515 mmol) and potassium carbonate (178 mg, 1.287 mmol) were dissolved in t-BuOH (5 mL) and Pd2dba3 (9.43 mg, 10.30 μmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (11.92 mg, 0.021 mmol) were added and then the reaction mixture was heated via microwave irradiation to 140° C. for 1 h. Reaction was monitored by TLC. After completion of the reaction, it was allowed to cool to about room temperature, and then reaction mixture was extracted with ethyl acetate (2×50 mL). The organic phase was concentrated and the residue was purified by flash column chromatography (4% MeOH/DCM) to provide the title compound (120 mg, 50.0% yield) as an off white solid. 1HNMR (400 MHz, CD3OD): δ 8.43 (s, 1H), 8.36 (s, 1H), 7.68 (m, 2H), 7.53 (d, 1H, J=2.0 Hz), 7.46 (t, 1H, J=8.4 Hz), 7.02 (dd, 1H, J=2.4 & 8.8 Hz), 6.97 (d, 1H, J=8.4 Hz), 6.50-6.38 (m, 2H), 5.80 (dd, 1H, J=2.4 & 9.6 Hz), 3.83 (m, 4H), 2.93 (m, 4H). Mass: 452.1 [M+H]+.

Workup

  1. customReaction
  2. customAfter completion of the reaction, it
  3. temperatureto cool to about room temperature
  4. customreaction mixture
  5. extractionwas extracted with ethyl acetate (2×50 mL)
  6. concentrationThe organic phase was concentrated
  7. customthe residue was purified by flash column chromatography (4% MeOH/DCM)

Sources & evidence

ORD record
ord-1defedeab39c4326ac27cf7976a94378
Source dataset
uspto-grants-2016_03
Patent number
US09296703B2

Reaction notes

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