Nitrogen → 3-(4-(1,1-dioxidothiomorpholino)-3-fluorophenyl)-2,6-dimethyl pyrimidin-4(3H)-one

HRID 56099Notes

Reaction equation

HRID 56099 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][S:11](=[O:15])(=[O:14])[CH2:10][CH2:9]2)=[C:4]([F:16])[CH:3]=1.C[Al](C)C.N#N.[NH:23](/[C:27](/[CH3:33])=[CH:28]\[C:29](OC)=[O:30])[C:24]([CH3:26])=O>C(Cl)Cl>[O:15]=[S:11]1(=[O:14])[CH2:12][CH2:13][N:8]([C:5]2[CH:6]=[CH:7][C:2]([N:1]3[C:29](=[O:30])[CH:28]=[C:27]([CH3:33])[N:23]=[C:24]3[CH3:26])=[CH:3][C:4]=2[F:16])[CH2:9][CH2:10]1

Participants

6

Reactant 4

HCID 947NitrogenHCID 57053602-Butenoic acid, 3-(acetylamino)-, methyl ester, (2Z)-HCID 16682925TrimethylaluminumHCID 435813994-(4-Amino-2-fluorophenyl)thiomorpholine 1,1-dioxide

Product 1

HCID 729482083-(4-(1,1-dioxidothiomorpholino)-3-fluorophenyl)-2,6-dimethyl pyrimidin-4(3H)-oneYield 47%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 4-(4-amino-2-fluorophenyl)1,1-dioxidothiomorpholine (1.20 g, 4.91 mmol) in anhydrous CH2Cl2 (100 mL) was added trimethylaluminium (28.5 mL, 28.5 mmol, 1 M in heptane) carefully dropwise under N2. Upon the end of addition the mixture was stirred at rt for 20 min, followed by the addition of a solution of methyl 3-acetaminocrotonate (2.32 g, 14.76 mmol) in anhydrous CH2Cl2 (30 mL). Upon the end of addition the reaction mixture was stirred at rt for another 15 h, then quenched with an appropriate amount of water and extracted with CH2Cl2. The combined organic phases were washed with brine, dried and concentrated in vacuo to give the title compound as a yellow solid (0.81 g, 47%). 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 15 h
  4. customquenched with an appropriate amount of water
  5. extractionextracted with CH2Cl2
  6. washThe combined organic phases were washed with brine
  7. customdried
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e05d37329d0140c7bd8c4f064bc5958b
Source dataset
uspto-grants-2016_09
Patent number
US09434695B2

Reaction notes

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