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

HRID 2274267Notes

Reaction equation

HRID 2274267 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:18]=[CH:19][C:20]([O:24][CH2:25][CH2:26][O:27][CH3:28])=[C:21]([OH:23])[CH:22]=3)[N:10]=2)[CH:5]=[CH:6][CH:7]=1.[C:29](Cl)(=[O:32])[CH:30]=[CH2:31].C1C=CC=CC=1.CC(C)=O.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:29](=[O:32])[CH:30]=[CH2:31])[CH:7]=[CH:6][CH:5]=2)=[N:10][C:11]([NH:16][C:17]2[CH:18]=[CH:19][C:20]([O:24][CH2:25][CH2:26][O:27][CH3:28])=[C:21]([OH:23])[CH:22]=2)=[N:12][CH:13]=1

Participants

7

Reactant 4

HCID 13140Acryloyl chlorideHCID 516892Sodium BicarbonateHCID 22015841Benzene methyl ketoneHCID 86724339HCID 86724339, compound

Product 1

HCID 86724340N-(3-((5-fluoro-2-((3-hydroxy-4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)acrylamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

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 5-((4-((3-aminophenyl)amino)-5-fluoropyrimidin-2-yl)amino)-2-(2-methoxyethoxy)phenol (0.17 g in 5 mL DCM) and cooled to −30° C. To the reaction mixture was slowly added acryloyl chloride solution in DCM (0.043 g in 5.0 mL DCM) and reaction mixture was stirred at −30° C. for 30 to 40 minutes. The reaction was monitored on TLC using benzene: acetone (8.5:1.5) as mobile phase. The reaction mixture was poured in water (100 mL) and basified using sodium bicarbonate. The solution was extracted with DCM (25 mL×2) and the combined organic layer was washed with 25 mL brine solution. The organic layer was dried over sodium sulfate and concentrated completely under reduce pressure at 40° C. Crude material was purified by preparative HPLC using 0.1% TFA in ACN and 0.1% TFA in water as mobile phase to give 23 mg of N-(3-((5-fluoro-2-((3-hydroxy-4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)acrylamide. M+1=439.3. 1H NMR: DMSO-d6 (400 MHz): 3.294 (s, 3H), 3.871-3.902 (t, 2H, J=6.0), 3.970-3.993 (t, 2H, J=4.4), 5.774-5.749 (d, 1H, J=10), 6.246-6.288 (d, 1H, J=16.8), 6.436-6.503 (m, 1H), 6.724-7.753 (d, 1H, J=11.6), 7.099 (s, 2H), 7.252-7.333 (m, 1H), 7.404-7.423 (d, 1H, J=7.6), 7.612-7.592 (d, 1H, J=8), 7.934 (s, 1H), 8.057-8.065 (d, 1H, J=3.2), 8.788 (s, 1H), 8.861 (s, 1H), 9.366 (s, 1H), 10.110 (s, 1H).

Workup

  1. customIn a 50 mL 3-neck RBF equipped with a magnetic stirrer, calcium chloride guard tube
  2. extractionThe solution was extracted with DCM (25 mL×2)
  3. washthe combined organic layer was washed with 25 mL brine solution
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. concentrationconcentrated completely
  6. customat 40° C
  7. customCrude material was purified by preparative HPLC

Sources & evidence

ORD record
ord-6b8e8de3ad3f42f5925acb04f0145981
Source dataset
uspto-grants-2015_09
Patent number
US09126950B2

Reaction notes

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