Dicyclohexylcarbodiimide → methyl N-(tert-butoxycarbonyl)-4-({N-[6-(2,5-dioxo-2,5-dihydro-1H pyrrol-1-yl)hexanoyl]glycyl}amino)-L-phenylalaninate

HRID 74829Notes

Reaction equation

HRID 74829 reaction equation
[NH2:1][C:2]1[CH:21]=[CH:20][C:5]([CH2:6][C@@H:7]([C:16]([O:18][CH3:19])=[O:17])[NH:8][C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])=[CH:4][CH:3]=1.C1(N=C=NC2CCCCC2)CCCCC1.[O:37]=[C:38]1[CH:42]=[CH:41][C:40](=[O:43])[N:39]1[CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][C:49]([NH:51][CH2:52][C:53](O)=[O:54])=[O:50]>CN(C)C=O>[C:12]([O:11][C:9]([NH:8][C@H:7]([C:16]([O:18][CH3:19])=[O:17])[CH2:6][C:5]1[CH:4]=[CH:3][C:2]([NH:1][C:53](=[O:54])[CH2:52][NH:51][C:49](=[O:50])[CH2:48][CH2:47][CH2:46][CH2:45][CH2:44][N:39]2[C:38](=[O:37])[CH:42]=[CH:41][C:40]2=[O:43])=[CH:21][CH:20]=1)=[O:10])([CH3:13])([CH3:14])[CH3:15]

Participants

5

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 110118554-Amino-N-((1,1-dimethylethoxy)carbonyl)-L-phenylalanine methyl esterHCID 71414224N-[6-(2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanoyl]glycine

Product 1

HCID 89573429methyl N-(tert-butoxycarbonyl)-4-({N-[6-(2,5-dioxo-2,5-dihydro-1H pyrrol-1-yl)hexanoyl]glycyl}amino)-L-phenylalaninateYield 32.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of methyl 4-amino-N-(tert-butoxycarbonyl)-L-phenylalaninate (4.1 g, 15.3 mmol, 1 eq.) in dry N,N-dimethylformamide (70 mL) was added N,N′-Dicyclohexylcarbodiimide (2.9 g, 15.3 mmol, 1 eq.) at 0° C. The mixture was stirred at 0° C. for 30 minutes. A solution of 2-(6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanamido)acetic acid (3 g, 10.2 mmol, 0.66 eq.) in dry N,N-dimethylformamide (20 mL) was added at 0° C. The mixture was stirred at room temperature for 3 days. The mixture was filtered. The filtrate was poured into ice water (200 mL) and extracted with EtOAc (200 mL×3). The extract was washed with brine (200 mL), dried over Na2SO4 and concentrated in vacuo to afford #251 (1.8 g, 32.3% yield) as a light yellow solid. HPLC (Protocol Q2) [M+Na+] 567.3, retention time=1.02 min

Workup

  1. stirringThe mixture was stirred at room temperature for 3 days
  2. filtrationThe mixture was filtered
  3. additionThe filtrate was poured into ice water (200 mL)
  4. extractionextracted with EtOAc (200 mL×3)
  5. washThe extract was washed with brine (200 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a21a5441e5fd45b2b57494bcd62bc790
Source dataset
uspto-grants-2014_09
Patent number
US08828401B2

Reaction notes

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