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 248083Notes

Reaction equation

HRID 248083 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 66%

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 (1.92 g, 6.52 mmol) in tetrahydrofuran (50 mL) and treat with N-methylmorpholine (0.77 mL, 6.52 mmol). Cool to -20° C. and treat with isobutyl chloroformate (0.86 mL, 6.52 mmol). Stir for 1 hour and add a solution of 1,3-dipropyl-5,6-diaminouracil (1.48 g, 6.52 mmol) in dimethylformamide (4 mL). Stir at -20° C. for 3 hours and warm to room temperature. Stir for 2 hours and dilute with chloroform (400 mL). Separate the organic phase and wash with saturated sodium hydrogen carbonate (300 mL), then brine (2×400 mL). Dry (Na2SO4) and evaporate the solvent in vacuo to give 4.31 g crude product. Purify by flash chromatography (10→15→20% isopropanol/hexane) to give the title compound (2.16 g, 66%); [α]d 20 =-45.8 ° (C=1.00, CHCl3).

Workup

  1. stirringStir at -20° C. for 3 hours
  2. temperaturewarm to room temperature
  3. stirringStir for 2 hours
  4. customSeparate the organic phase
  5. washwash with saturated sodium hydrogen carbonate (300 mL)
  6. dry with materialDry (Na2SO4)
  7. customevaporate the solvent in vacuo
  8. customto give 4.31 g crude product
  9. customPurify by flash chromatography (10→15→20% isopropanol/hexane)

Sources & evidence

ORD record
ord-a39cd05938774da58bb639e6c98ab8b9
Source dataset
uspto-grants-1993_05
Patent number
US05208240

Reaction notes

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