Nitrogen → 3-(3-fluoro-4-thiomorpholinophenyl)-2,6-dimethylpyrimidin-4(3H)-one

HRID 56096Notes

Reaction equation

HRID 56096 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[N:9]1[CH2:14][CH2:13][S:12][CH2:11][CH2:10]1)[NH2:5].C[Al](C)C.N#N.[NH:21](/[C:25](/[CH3:31])=[CH:26]\[C:27](OC)=[O:28])[C:22]([CH3:24])=O>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([N:5]2[C:27](=[O:28])[CH:26]=[C:25]([CH3:31])[N:21]=[C:22]2[CH3:24])[CH:6]=[CH:7][C:8]=1[N:9]1[CH2:10][CH2:11][S:12][CH2:13][CH2:14]1

Participants

6

Reactant 4

HCID 947NitrogenHCID 57053602-Butenoic acid, 3-(acetylamino)-, methyl ester, (2Z)-HCID 108224433-Fluoro-4-thiomorpholinoanilineHCID 16682925Trimethylaluminum

Product 1

HCID 729482063-(3-fluoro-4-thiomorpholinophenyl)-2,6-dimethylpyrimidin-4(3H)-oneYield 67%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 3-fluoro-4-thiomorpholinoaniline (1.20 g, 5.65 mmol) in anhydrous CH2Cl2 (60 mL) was added trimethylaluminium (28.5 mL, 28.5 mmol, 1 M in heptane) carefully dropwise under the protection of N2. Upon the end of addition the mixture was stirred at rt for 40 min, followed by the addition of a solution of methyl 3-acetaminocrotonate (2.66 g, 16.92 mmol) in anhydrous CH2Cl2 (20 mL). Upon the end of addition the reaction mixture was stirred at rt for another 6 h, then quenched with water and extracted with CH2Cl2. The combined organic phases were washed with brine, dried over anhydrous Na2SO4 and concentrated in vacuo to give the title compound as pale yellow solid (0.91 g, 67%). The compound was characterized by the following spectroscopic data:

Workup

  1. additionUpon the end of addition the mixture
  2. additionUpon the end of addition the reaction mixture
  3. stirringwas stirred at rt for another 6 h
  4. customquenched with water
  5. extractionextracted with CH2Cl2
  6. washThe combined organic phases were washed with brine
  7. dry with materialdried over anhydrous Na2SO4
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-09b742dfdf984ca696fab087f38f147d
Source dataset
uspto-grants-2016_09
Patent number
US09434695B2

Reaction notes

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