Acryloyl chloride → N-(3-((5-fluoro-2-((4-((2-methoxyethoxy)methoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)acrylamide

HRID 2274249Notes

Reaction equation

HRID 2274249 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[C:14]([F:15])=[CH:13][N:12]=[C:11]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][CH2:24][O:25][CH2:26][CH2:27][O:28][CH3:29])=[CH:19][CH:18]=3)[N:10]=2)[CH:5]=[CH:6][CH:7]=1.[C:30](Cl)(=[O:33])[CH:31]=[CH2:32].C(Cl)(Cl)Cl.CO.C(=O)(O)[O-].[Na+]>C(Cl)Cl.O>[F:15][C:14]1[C:9]([NH:8][C:4]2[CH:3]=[C:2]([NH:1][C:30](=[O:33])[CH:31]=[CH2:32])[CH:7]=[CH:6][CH:5]=2)=[N:10][C:11]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH2:24][O:25][CH2:26][CH2:27][O:28][CH3:29])=[CH:19][CH:18]=2)=[N:12][CH:13]=1

Participants

7

Reactant 4

HCID 13140Acryloyl chlorideHCID 516892Sodium BicarbonateHCID 21584188Chloroform methanolHCID 86724329N4-(3-aminophenyl)-5-fluoro-N2-(4-((2-methoxyethoxy)methoxy)phenyl)pyrimidine-2,4-diamine

Product 1

HCID 86724330N-(3-((5-fluoro-2-((4-((2-methoxyethoxy)methoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)acrylamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-30 °C

Procedure

In a 50 mL, 3-neck RBF equipped with a magnetic stirrer, calcium chloride guard tube and thermo pocket was charged N4-(3-aminophenyl)-5-fluoro-N2-(4-((2-methoxyethoxy)methoxy)phenyl)pyrimidine-2,4-diamine (0.380 g) in DCM (10 mL) and was cooled to −30° C. To the reaction mixture was slowly added acryloyl chloride solution in DCM (0.090 g in 5.0 mL DCM) and the reaction mixture was stirred at −30° C. for approx. 40 minutes. The reaction was monitored on TLC using chloroform:methanol (9.6:0.4) as mobile phase. The reaction mixture was poured into water (100 mL) and basified using sodium bicarbonate. The reaction mixture was extracted with DCM (25 mL×2) and the combined organic layers were washed with 50 mL brine solution. The organic layer was dried over sodium sulfate and concentrated completely under reduce pressure at 40° C. The crude product was purified by column chromatography eluting in 35% of ethyl acetate in hexane to give 0.36 g of N-(3-((5-fluoro-2-((4-((2-methoxyethoxy)methoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)acrylamide.

Workup

  1. customIn a 50 mL, 3-neck RBF equipped with a magnetic stirrer, calcium chloride guard tube
  2. extractionThe reaction mixture was extracted with DCM (25 mL×2)
  3. washthe combined organic layers were washed with 50 mL brine solution
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. concentrationconcentrated completely
  6. customat 40° C
  7. customThe crude product was purified by column chromatography
  8. washeluting in 35% of ethyl acetate in hexane

Sources & evidence

ORD record
ord-04d17d56b26b45b39f53f4dfc2d07552
Source dataset
uspto-grants-2015_09
Patent number
US09126950B2

Reaction notes

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