4-Methylmorpholine → Tert-butyl 2-[4-[3-[(4-amino-2,6-dioxo-1,3-dipropylpyrimidin-5-yl)amino]-2-methyl-3-oxopropyl]phenoxy]acetate

HRID 248080Notes

Reaction equation

HRID 248080 reaction equation
[CH3:1][C:2]([CH3:21])([O:4][C:5](=[O:20])[CH2:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([CH2:14][CH:15]([CH3:19])[C:16]([OH:18])=O)=[CH:10][CH:9]=1)[CH3:3].CN1CCOCC1.ClC(OCC(C)C)=O.[CH2:37]([N:40]1[C:47]([NH2:48])=[C:46]([NH2:49])[C:44](=[O:45])[N:43]([CH2:50][CH2:51][CH3:52])[C:41]1=[O:42])[CH2:38][CH3:39]>O1CCCC1.CN(C)C=O.C(Cl)(Cl)Cl>[NH2:48][C:47]1[N:40]([CH2:37][CH2:38][CH3:39])[C:41](=[O:42])[N:43]([CH2:50][CH2:51][CH3:52])[C:44](=[O:45])[C:46]=1[NH:49][C:16](=[O:18])[CH:15]([CH3:19])[CH2:14][C:11]1[CH:10]=[CH:9][C:8]([O:7][CH2:6][C:5]([O:4][C:2]([CH3:1])([CH3:3])[CH3:21])=[O:20])=[CH:13][CH:12]=1

Participants

8

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 50986055,6-Diamino-1,3-dipropyl-2,4(1H,3H)-pyrimidinedioneHCID 197645314-[[2-(1,1-Dimethylethoxy)-2-oxoethyl]oxy]-alpha-methyl-benzenepropanoic acid

Product 1

HCID 45118932Tert-butyl 2-[4-[3-[(4-amino-2,6-dioxo-1,3-dipropylpyrimidin-5-yl)amino]-2-methyl-3-oxopropyl]phenoxy]acetateYield 72.5%

Reagents, catalysts & solvents 3

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

Dissolve (+)-4-[[2-(1,1-dimethylethoxy)-2-oxoethyl]oxy]-alpha-methyl-benzenepropanoic acid (3.02 g, 10.27 mmol) in tetrahydrofuran (100 mL) and treat with N-methylmorpholine (1.2 mL, 10.27 mmol). Cool to -20° C., add isobutyl chloroformate (1.35 mL, 10.27 mmol) and stir for 1 hour. Add a solution of 1,3-dipropyl-5,6-diaminouracil (2.33 g, 10.27 mmol) in dimethylformamide (8 mL) and stir for 6 hours at -20° C. Warm to room temperature and dilute with chloroform (600 mL). Wash with saturated sodium hydrogen carbonate (300 mL), then brine (3×300 mL). Dry (MgSO4) and evaporate the solvent in vacuo. Purify by flash chromatography (5→10→15→20% isopropanyl/hexane) to give the title compound as a foam (3.74 g, 72%); [α]d 20 =+51.4° (C=1.03, CHCl3).

Workup

  1. stirringstir for 6 hours at -20° C
  2. temperatureWarm to room temperature
  3. washWash with saturated sodium hydrogen carbonate (300 mL)
  4. dry with materialDry (MgSO4)
  5. customevaporate the solvent in vacuo
  6. customPurify by flash chromatography (5→10→15→20% isopropanyl/hexane)

Sources & evidence

ORD record
ord-081ea15d782e44b08dea08e8005abcaa
Source dataset
uspto-grants-1993_05
Patent number
US05208240

Reaction notes

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