Dichloromethane → N-[2-(3,4-Dihydro-5-methyl-2,4-dioxo-1(2H)-pyrimidinyl)acetyl]-N-[2-[[(1,1-dimethylethoxy)carbonyl]amino]ethyl]glycine 2,3,4,5,6-pentafluorophenyl ester

HRID 1354516Notes

Reaction equation

HRID 1354516 reaction equation
[C:1]([NH:8][CH2:9][CH2:10][N:11]([C:16](=[O:27])[CH2:17][N:18]1[CH:26]=[C:24]([CH3:25])[C:22](=[O:23])[NH:21][C:19]1=[O:20])[CH2:12][C:13]([OH:15])=[O:14])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C(Cl)Cl.[F:31][C:32]1[C:37](O)=[C:36]([F:39])[C:35]([F:40])=[C:34]([F:41])[C:33]=1[F:42]>CN(C=O)C>[F:31][C:32]1[C:37]([O:14][C:13](=[O:15])[CH2:12][N:11]([CH2:10][CH2:9][NH:8][C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[C:16](=[O:27])[CH2:17][N:18]2[CH:26]=[C:24]([CH3:25])[C:22](=[O:23])[NH:21][C:19]2=[O:20])=[C:36]([F:39])[C:35]([F:40])=[C:34]([F:41])[C:33]=1[F:42]

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 13041PentafluorophenolHCID 4070836HCID 4070836, compound

Product 1

HCID 11180378N-[2-(3,4-Dihydro-5-methyl-2,4-dioxo-1(2H)-pyrimidinyl)acetyl]-N-[2-[[(1,1-dimethylethoxy)carbonyl]amino]ethyl]glycine 2,3,4,5,6-pentafluorophenyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

N-(N-Boc-2-aminoethyl)-N-[(1-thyminyl)acetyl]glycine (5) (2.00 g; 5.20 mmol) was dissolved in DMF (5 ml) and methylene chloride (15 ml) was added. Pentafluorophenol (1.05 g; 5.72 mmol) was added and the solution was cooled to 0° C. in an ice bath. DDC then was added (1.29 g; 6.24 mmol) and the ice bath was removed after 2 min. After 3 h with stirring at ambient temperature, the precipitated DCU was removed by filtration and washed with methylene chloride. The combined filtrate was washed twice with aqueous sodium hydrogen carbonate and once with saturated sodium chloride, dried over magnesium sulfate, and evaporated to dryness, in vacuo. The solid residue was dissolved in dioxane (150 ml) and poured into water (200 ml) at 0° C. The title compound was isolated by filtration, washed with water, and dried over an appropriate drying agent, in vacuo. Yield: 2.20 g (77%). An analytical sample was obtained by recrystallisation from 2-propanol. M.p. 174–175.5° C. Analysis for C22H23N4O7F5, found(calc.): C, 48.22(48.01); H: 4.64(4.21); N: 9.67(10.18). 1H-NMR (250 MHz, CDCl3):Due to the limited rotation around the secondary amide bond several of the signals were doubled in the ratio 6:1 (indicated in the list by mj. for major and mi. for minor). 7.01 ppm (s, mi., ArH); 6.99 ppm (s, mj., ArH); 5.27 ppm (unres. t, BocNH); 4.67 ppm (s, mj., T-CH2—CO—); 4.60 ppm (s, mi., T-CH2—CO—); 4.45 ppm (s, mj., CONRCH2CO2Pfp); 4.42 ppm (s, mi., CONRCH2CO2Pfp); 3.64 ppm (t,2H,BocNHCH2CH2-); 3.87 ppm (“q”,2H,BocNHCH2CH2—); 1.44(s,9H,t-Bu). FAB-MS: 551 (10; M+1); 495 (10; M+1-tBu); 451 (80; -Boc).

Workup

  1. additionDDC then was added (1.29 g; 6.24 mmol)
  2. customthe ice bath was removed after 2 min
  3. customthe precipitated DCU was removed by filtration
  4. washwashed with methylene chloride
  5. washThe combined filtrate was washed twice with aqueous sodium hydrogen carbonate and once with saturated sodium chloride
  6. dry with materialdried over magnesium sulfate
  7. customevaporated to dryness, in vacuo
  8. dissolutionThe solid residue was dissolved in dioxane (150 ml)
  9. additionpoured into water (200 ml) at 0° C

Sources & evidence

ORD record
ord-a39ebda449dd4b309c48ff74a33fac9e
Source dataset
uspto-grants-2007_05
Patent number
US07223833B1

Reaction notes

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