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

HRID 1500803Notes

Reaction equation

HRID 1500803 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.[F:20][C:21]1[CH:22]=[C:23]([CH:25]=[CH:26][C:27]=1[N:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1)[NH2:24].C([O-])([O-])=O.[Cs+].[Cs+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>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:24][C:23]2[CH:25]=[CH:26][C:27]([N:28]3[CH2:29][CH2:30][O:31][CH2:32][CH2:33]3)=[C:21]([F:20])[CH:22]=2)=[N:3][CH:4]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 14853303-Fluoro-4-morpholinoanilineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 71469246N-(3-(2,5-dichloropyrimidin-4-yl)phenyl)acrylamide

Product 1

HCID 68384949N-(3-(5-chloro-2-((3-fluoro-4-morpholinophenyl)amino)pyrimidin-4-yl)phenyl)acrylamideYield 32.9%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
200 °C

Procedure

N-(3-(2,5-dichloropyrimidin-4-yl)phenyl)acrylamide (50 mg, 0.170 mmol), 3-fluoro-4-morpholinoaniline (33.4 mg, 0.170 mmol) and Cs2CO3 (66.5 mg, 0.204 mmol) were dissolved in toluene (5 ml) in a sealable microwave compatible reaction tube, then Pd2(dba)3 (3.11 mg, 3.40 μmol) and X-phos (3.93 mg, 6.80 μmol) were added. The reaction tube was sealed and the reaction was heated under microwave irradiation (60 min, 200° C., 3 atm). The reaction was monitored by TLC and after completion of the reaction, the solvent was in vacuo. The compound was purified by column chromatography (10% CH3OH/CH2Cl2) to yield N-(3-(5-chloro-2-((3-fluoro-4-morpholinophenyl)amino)pyrimidin-4-yl)phenyl)acrylamide (26 mg, 0.056 mmol, 32.7% yield) as a solid. 1H NMR (400 MHz, CD3OD): δ 8.43 (s, 1H), 8.22 (s, 1H), 7.75 (d, 1H, J=7.2 Hz), 7.65-7.57 (m, 2H), 7.45 (t, 1H, J=8.0 Hz), 7.34 (m, 1H), 6.94 (t, 1H, J=9.2 Hz), 6.40 (m, 2H), 5.78 (dd, 1H, J=2.0 & 9.6 Hz), 3.80 (m, 4H), 2.98 (m, 4H). ESI-MS: m/z 454.1 [M+H]+.

Workup

  1. customThe reaction tube was sealed
  2. customafter completion of the reaction
  3. customThe compound was purified by column chromatography (10% CH3OH/CH2Cl2)

Sources & evidence

ORD record
ord-c8d5e91129584a41b9773b7f82bbaf43
Source dataset
uspto-grants-2015_12
Patent number
US09206176B2

Reaction notes

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