Cesium carbonate → N-(3-(5-chloro-2-((4-morpholinophenyl)amino)pyrimidin-4-yl)phenyl)acrylamide

HRID 1500799Notes

Reaction equation

HRID 1500799 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.[O:20]1[CH2:25][CH2:24][N:23]([C:26]2[CH:32]=[CH:31][C:29]([NH2:30])=[CH:28][CH:27]=2)[CH2:22][CH2:21]1.C([O-])([O-])=O.[Cs+].[Cs+].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>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[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:30][C:29]2[CH:28]=[CH:27][C:26]([N:23]3[CH2:24][CH2:25][O:20][CH2:21][CH2:22]3)=[CH:32][CH:31]=2)=[N:3][CH:4]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 75655Benzenamine, 4-(4-morpholinyl)-HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 71469246N-(3-(2,5-dichloropyrimidin-4-yl)phenyl)acrylamide

Product 1

HCID 68384955N-(3-(5-chloro-2-((4-morpholinophenyl)amino)pyrimidin-4-yl)phenyl)acrylamide

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
200 °C

Procedure

N-(3-(2,5-dichloropyrimidin-4-yl)phenyl)acrylamide (25 mg, 0.085 mmol), 4-morpholinoaniline (15.15 mg, 0.085 mmol) and Cs2CO3 (27.7 mg, 0.085 mmol) were dissolved in toluene (4.5 ml) in a sealable microwave compatible reaction tube, and then Pd2 dba3 (1.557 mg, 1.700 mmol) and 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene (1.967 mg, 3.40 mmol) were added. The reaction tube was sealed and the reaction was heated under microwave irradiation (30 min, 200° C., 3 atm). The reaction was monitored by TLC. After completion of the reaction, solvent was removed in vacuo. The product was purified by flash column chromatography (5% CH3OH/CH2Cl2) to give the title compound. 1H NMR (400 MHz, CD3OD): δ 8.23 (s, 1H), 7.66 (m, 1H), 7.56 (s, 1H), 7.45-7.39 (m, 1H), 7.20 (m, 2H), 6.93 (m, 1H), 6.70 (m, 2H), 6.46-6.34 (m, 2H), 5.78 (dd, 1H, J=2.0 & 9.6 Hz), 3.80 (m, 4H), 2.99 (m, 4H). ESI-MS: 436.07 [M+H]+.

Workup

  1. customThe reaction tube was sealed
  2. customAfter completion of the reaction, solvent
  3. customwas removed in vacuo
  4. customThe product was purified by flash column chromatography (5% CH3OH/CH2Cl2)

Sources & evidence

ORD record
ord-b4b46b52a79642bc89ae48c38e229df5
Source dataset
uspto-grants-2015_12
Patent number
US09206176B2

Reaction notes

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