Piperidine → N-[2-chloro-4-[[[(3-hydroxyphenyl) methyl]amino]carbonyl]benzoyl]-3-[(2-propenyloxy)carbonyl]amino-L-alanine

HRID 2270824Notes

Reaction equation

HRID 2270824 reaction equation
C1C2C(COC([NH:18][C@H:19]([C:28]([OH:30])=[O:29])[CH2:20][NH:21][C:22]([O:24][CH2:25][CH:26]=[CH2:27])=[O:23])=O)C3C(=CC=CC=3)C=2C=CC=1.N1CCCCC1.[Cl:37][C:38]1[CH:46]=[C:45]([C:47]([NH:49][CH2:50][C:51]2[CH:56]=[CH:55][CH:54]=[C:53]([OH:57])[CH:52]=2)=[O:48])[CH:44]=[CH:43][C:39]=1[C:40]([OH:42])=O.C1C=NC2N(O)N=NC=2C=1>CN1CCCC1=O>[Cl:37][C:38]1[CH:46]=[C:45]([C:47]([NH:49][CH2:50][C:51]2[CH:56]=[CH:55][CH:54]=[C:53]([OH:57])[CH:52]=2)=[O:48])[CH:44]=[CH:43][C:39]=1[C:40]([NH:18][C@H:19]([C:28]([OH:30])=[O:29])[CH2:20][NH:21][C:22]([O:24][CH2:25][CH:26]=[CH2:27])=[O:23])=[O:42]

Participants

6

Reactant 4

HCID 8082PiperidineHCID 181649HOAtHCID 2756107Fmoc-Dap(Alloc)-OHHCID 226613972-Chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoic acid

Product 1

HCID 68820330N-[2-chloro-4-[[[(3-hydroxyphenyl) methyl]amino]carbonyl]benzoyl]-3-[(2-propenyloxy)carbonyl]amino-L-alanine

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent2×

Procedure

A150 mL cylidrical glass vessel equipped with a coarse glass frit was charged with N-[(9H-fluoren-9-ylmethoxy)carbonyl]-3-[(2-propenyloxy)carbonyl]amino-L-alanine resin (Example 64; 5 g) and 25% piperidine in N-methylpyrrolidinone (50 mL). The mixture was agitated at room temperature for 30 min. The resin was filtered and treated again with fresh 25% piperidine in N-methylpyrrolidinone (50 mL) at room temperature for 30 min. After filtration, the resin was washed with dichloromethane and methanol. To the resin was added a solution prepared from 2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoic acid (Example 26; 2.5 g, 8.2 mmol), HOAT (3.7 g, 27.2 mmol) and DICI (4.3 mL, 27.5 mmol) in N-methylpyrrolidinone (50 mL). The reaction mixture was agitated at room temperature for 1 h, and then filtered. The resin was washed with dichloromethane and methanol, and dried under vacuum to afford resin-bound N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[(2-propenyioxy) carbonyl]amino-L-alanine.

Workup

  1. customA150 mL cylidrical glass vessel equipped with a coarse glass frit
  2. filtrationThe resin was filtered
  3. additiontreated again with fresh 25% piperidine in N-methylpyrrolidinone (50 mL) at room temperature for 30 min
  4. filtrationAfter filtration
  5. washthe resin was washed with dichloromethane and methanol
  6. additionTo the resin was added a solution
  7. stirringThe reaction mixture was agitated at room temperature for 1 h
  8. filtrationfiltered
  9. washThe resin was washed with dichloromethane and methanol
  10. customdried under vacuum

Sources & evidence

ORD record
ord-a365aa00e0c9468b9b41a1ef1136fb9c
Source dataset
uspto-grants-2001_12
Patent number
US06331640B1

Reaction notes

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