Uracil → 2,4-dioxo-N-(5-phenylpentyl)pyrimidine-1-carboxamide

HRID 1486559Notes

Reaction equation

HRID 1486559 reaction equation
[C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][NH2:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:13]([O-:16])(O)=O.[Na+].ClC(Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl.[NH:30]1[CH:37]=[CH:36][C:34](=[O:35])[NH:33][C:31]1=[O:32]>ClCCl.C1(C)C=CC=CC=1.CN(C1C=CN=CC=1)C.N1C=CC=CC=1>[O:32]=[C:31]1[NH:33][C:34](=[O:35])[CH:36]=[CH:37][N:30]1[C:13]([NH:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)=[O:16]

Participants

9

Reactant 4

HCID 1174UracilHCID 94429TriphosgeneHCID 140275BenzenepentanamineHCID 516892Sodium Bicarbonate

Product 1

HCID 725489752,4-dioxo-N-(5-phenylpentyl)pyrimidine-1-carboxamideYield 32%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

5-phenylpentan-1-amine (0.07 g, 0.43 mmol) was dissolved in dry dichloromethane (4.5 mL). The solution was cooled to 0° C. and saturated aqueous NaHCO3 solution (4.5 mL) was added. The biphasic mixture was stirred for 10 min at 0° C., the layers were allowed to separate then a solution of triphosgene (0.51 g, 0.52 mmol) in dry toluene (2.5 mL) was added to the organic layer. After 15 min the aqueous layer was extracted with dichloromethane (3×10 mL). The combined organic layers were dried over Na2SO4 and the solvent was removed under reduced pressure. The resulting residue was added to a solution of uracil (0.05 g, 0.43 mmol) and DMAP (0.01 g, 0.01 mmol) in dry pyridine (5 mL). The suspension was stirred at room temperature for 18 hrs. The crude was purified by column chromatography using a Teledyne ISCO apparatus (cyclohexane:EtOAc 75:25) to afford the title compound (0.04 g, 32%) as a white solid. 1H NMR (400 MHz, DMSO-d6): 1.25-1.42 (m, 2H), 1.46-1.64 (m, 5H), 2.54-2.60 (m, 2H), 3.21-3.28 (m, 2H), 5.79 (d, J=8.38 Hz, 1H), 7.06-7.36 (m, 5H), 8.20 (d, J=8.40 Hz, 1H), 9.11 (t, J=5.65 Hz, 1H), 11.71 (s, 1H). 13C NMR (101 MHz, DMSO-d6) δ 26.18, 28.56, 30.79, 35.12, 41.81, 40.26, 103.48, 125.78, 128.11, 129.30, 139.70, 149.23, 151.13, 161.80.

Workup

  1. customto separate
  2. extractionAfter 15 min the aqueous layer was extracted with dichloromethane (3×10 mL)
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. customthe solvent was removed under reduced pressure
  5. stirringThe suspension was stirred at room temperature for 18 hrs
  6. customThe crude was purified by column chromatography

Sources & evidence

ORD record
ord-80f52ac71ba54ad6949c6c5cdc1daa43
Source dataset
uspto-grants-2016_08
Patent number
US09428465B2

Reaction notes

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