Acetyl chloride → HCID 22049884, compound

HRID 1866959Notes

Reaction equation

HRID 1866959 reaction equation
Cl.[NH2:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[C:12]([Br:24])[C:11]2=[O:25])=[CH:6][CH:5]=1.CN1CC[O:30][CH2:29][CH2:28]1.C(Cl)(=O)C.CN=C=O>CN(C)C=O.ClCCl>[CH2:17]([O:16][C:13]1[CH:14]=[CH:15][N:10]([C:7]2[CH:8]=[CH:9][C:4]([CH2:3][NH:2][C:29](=[O:30])[CH3:28])=[CH:5][CH:6]=2)[C:11](=[O:25])[C:12]=1[Br:24])[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

7

Reactant 4

HCID 6367Acetyl chlorideHCID 79724-MethylmorpholineHCID 12228Methyl IsocyanateHCID 22050088HCID 22050088, compound

Product 1

HCID 22049884HCID 22049884, compoundYield 50%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent3×HCID 6344DichloromethaneSolvent

Procedure

1-[4-(aminomethyl)phenyl]-4-(benzyloxy)-3-bromopyridin-2(1H)-one hydrochloride (0.150 g, 0.389 mmol) was dissolved in N,N-dimethylformamide (3.5 mL). A stock solution of 4-methylmorpholine in N,N-dimethylformamide (1.5 mL, 1.0 M) was added and the reaction stirred at room temperature for 10 minutes. A stock solution of acetyl chloride in N,N-dimethylformamide (3.0 mL, 0.2 M) was then added to the reaction vessel and the reaction apparatus was orbitally shaken at 200 RPM for 2 hours at room temperature. At this time the reaction was diluted with dichloromethane (4 mL) and treated with approximately 1.8 g of polyamine resin (2.63 mmol/g) and approximately 0.8 g of methylisocyanate functionalized polystyrene (1.7 mmol/g) and the orbital shaking was continued at 200 RPM at room temperature overnight. The reaction vessel was then opened and the solution phase products were separated from the insoluble quenched byproducts by filtration and collection into a vial. After partial evaporation the insoluble byproducts were further rinsed with dichloromethane (3×5 mL) and combined with the partially concentrated filtrate. The resulting filtrate was concentrated by blowing N2 over the vial while heating (60° C.) in a reaction block (KEM-Lab Parallel Reactor) to give an off-white solid (0.083 g, 50%). 1H NMR (400 MHz, CD3OD) δ 7.59 (d, J=7.79 Hz, 1H), 7.48-7.29 (m, 9H), 6.55 (d, J=7.79 Hz, 1H), 5.35 (s, 2H), 4.39 (s, 2H), 1.98 (s, 3H). ES-HRMS m/z 427.0625 (M+H C21H19BrN2O3 requires 427.0652).

Workup

  1. stirringthe reaction apparatus was orbitally shaken at 200 RPM for 2 hours at room temperature
  2. stirringthe orbital shaking
  3. waitwas continued at 200 RPM at room temperature overnight
  4. customthe solution phase products were separated from the insoluble quenched byproducts by filtration and collection into a vial
  5. customAfter partial evaporation the insoluble byproducts
  6. washwere further rinsed with dichloromethane (3×5 mL)
  7. concentrationThe resulting filtrate was concentrated
  8. temperatureheating (60° C.) in a reaction block (KEM-Lab Parallel Reactor)

Sources & evidence

ORD record
ord-fb342f3fc89a4f3f836581b163a8e821
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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