Water → 3-(3-fluoro-4-((2-morpholinoethyl)amino)phenyl)-2-((3-fluorophenoxy)methyl)-6-methylpyrimidin-4(3H)-one

HRID 56263Notes

Reaction equation

HRID 56263 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([NH2:8])[CH:5]=[CH:4][C:3]=1[NH:9][CH2:10][CH2:11][N:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1.C[Al](C)C.C[O:23][C:24](=O)/[CH:25]=[C:26](\[NH:28][C:29](=O)[CH2:30][O:31][C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[CH:33]=1)/[CH3:27].O>C(Cl)Cl>[F:1][C:2]1[CH:7]=[C:6]([N:8]2[C:24](=[O:23])[CH:25]=[C:26]([CH3:27])[N:28]=[C:29]2[CH2:30][O:31][C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[CH:33]=2)[CH:5]=[CH:4][C:3]=1[NH:9][CH2:10][CH2:11][N:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1

Participants

6

Reactant 4

HCID 962WaterHCID 16682925TrimethylaluminumHCID 176096902-fluoro-N1-(2-morpholinoethyl)benzene-1,4-diamineHCID 90022556Methyl 3-(2-(3-fluorophenoxy)acetamido)crotonate

Product 1

HCID 900314133-(3-fluoro-4-((2-morpholinoethyl)amino)phenyl)-2-((3-fluorophenoxy)methyl)-6-methylpyrimidin-4(3H)-oneYield 79.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-fluoro-N1-(2-morpholinoethyl)benzene-1,4-diamine (0.33 g, 1.38 mmol) in DCM (20 mL) was added trimethylaluminium (2.1 mL, 4.2 mmol, 2 M in toluene) slowly and the mixture was stirred at rt for 0.5 h. A solution of (Z)-methyl-3-(2-(3-fluorophenoxy)acetamido)but-2-enoate (0.37 g, 1.38 mmol) in DCM (5 mL) was added slowly and the resulting mixture was stirred at rt for 24 h. 50 mL of water was then added to the mixture slowly and the mixture was extracted with CH2Cl2 (50 mL×2). The combined organic phases were washed with brine (100 mL×3), dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (EtOAc) to give the title compound as a pale yellow solid (0.5 g, 79%). The compound was characterized by the following spectroscopic data:

Workup

  1. stirringthe resulting mixture was stirred at rt for 24 h
  2. extractionthe mixture was extracted with CH2Cl2 (50 mL×2)
  3. washThe combined organic phases were washed with brine (100 mL×3)
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by a silica gel column chromatography (EtOAc)

Sources & evidence

ORD record
ord-5039eba7e6064f93b17f0bea4b9ad88e
Source dataset
uspto-grants-2016_09
Patent number
US09434695B2

Reaction notes

Loading…