1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 86687794, compound

HRID 926811Notes

Reaction equation

HRID 926811 reaction equation
[C:1]([NH:6][CH2:7][C:8]([NH:10][C@H:11]([C:19]([NH:21][C@H:22]([C:27]([NH:29][CH2:30][C:31]([OH:33])=O)=[O:28])[CH2:23][CH:24]([CH3:26])[CH3:25])=[O:20])[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:9])(=[O:5])[C:2]([CH3:4])=[CH2:3].[SH:34][C:35]1[S:36][CH2:37][CH2:38][N:39]=1.CCN=C=NCCCN(C)C>CN(C1C=CN=CC=1)C.ClCCl>[C:1]([NH:6][CH2:7][C:8]([NH:10][C@H:11]([C:19]([NH:21][C@H:22]([C:27]([NH:29][CH2:30][C:31]([N:39]1[CH2:38][CH2:37][S:36][C:35]1=[S:34])=[O:33])=[O:28])[CH2:23][CH:24]([CH3:25])[CH3:26])=[O:20])[CH2:12][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)=[O:9])(=[O:5])[C:2]([CH3:4])=[CH2:3]

Participants

6

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 54174764N-(2-Methylacryloyl)glycyl-L-phenylalanyl-L-leucylglycineHCID 178527880HCID 178527880, compound

Product 1

HCID 86687794HCID 86687794, compoundYield 51.9%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-10 °C

Procedure

The synthesis of MA-GFLG-TT followed a published procedure [V. {hacek over (S)}ubr et al., Reactive & Functional Polymers 66 1525-1538 (2006)] with a slight modification. Under nitrogen atmosphere, N-methacryloylglycylphenylalanylleucylglycine (MA-GFLG-OH; 320 mg, 0.7 mmol), 2-mercaptothiazoline (83.5 mg, 0.7 mmol) and DMAP (85.5 mg, 0.7 mmol) were dissolved in dichloromethane (DCM) (20 mL). The solution was stirred for 5 min −10° C., EDCI (134.2 mg, 0.7 mmol) was added and the solution was stirred −10° C. for 3 h and at room temperature for another 12 h. After reaction, 50 mL DCM was added, the solution was washed with NaHCO3 aq. (0.1 M), HCl (0.1 M) and then NaCl aq. The organic layer was dried (MgSO4), solvent removed by rotary evaporation and the crude product was purified by column chromatography (silica gel 60 Å, 200-400 mesh, EtOAc: CH3OH, 15:1) and then recrystallized from DCM to give yellow powder in 51.9% yield. The structure was confirmed by 1H NMR and 13C NMR spectroscopy. 1H NMR (300 MHz, CDCl3, δ in ppm): 0.86 (m, 6 H, CH(CH3)2), 1.51 (m, 2H, CHCH2CH(CH3)2), 1.66 (m, 1H, CH(CH3)2), 1.91 (s, 3 H, CCH3), 3.03 (m, 2 H, Ph-CH2), 3.33 (t, 2 H, SCH2), 4.00 (s, 2 H, NHCH2CO), 4.54 (t, 2 H, NCH2CH2S), 4.63 (m, 1 H, NHCHCO), 4.73 (m, 1 H, NHCHCO), 4.81 (s, 2 H, NHCH2CO), 5.39 (s, 1H, C═CH2), 5.77 (s, 1H, C═CH2), 6.99 (s, 1 H, NH), 7.18 (m, 6 H, NH, Ph-H), 7.56-7.80 (m, 2 H, NH). 13C NMR (75 MHz, CDCl3, δ in ppm): 201.78, 172.6, 170.92, 170.57, 169.33, 168.99, 139.02, 136.46, 129.77, 128.80, 127.21, 121.31, 56.11, 54.89, 51.83, 46.85, 43.61, 41.81, 39.37, 29.37, 24.88, 22.86, 18.21.

Workup

  1. customThe synthesis of MA-GFLG-TT
  2. additionwas added
  3. additionwas added
  4. washthe solution was washed with NaHCO3 aq. (0.1 M), HCl (0.1 M)
  5. dry with materialNaCl aq. The organic layer was dried (MgSO4), solvent
  6. customremoved by rotary evaporation
  7. customthe crude product was purified by column chromatography (silica gel 60 Å, 200-400 mesh, EtOAc: CH3OH, 15:1)
  8. customrecrystallized from DCM
  9. customto give yellow powder in 51.9% yield

Sources & evidence

ORD record
ord-f17762da6f69470b888b6cbeea1ee635
Source dataset
uspto-grants-2016_03
Patent number
US09289510B2

Reaction notes

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