2-Thiophenecarboxylic acid → N-[2-chloro-4-[[(2,3-dihydro-1H-indol-4-ylmethyl)amino]carbonyl]benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine

HRID 393072Notes

Reaction equation

HRID 393072 reaction equation
[NH2:1][CH2:2][C@@H:3]([C:27]([OH:29])=[O:28])[NH:4][C:5](=[O:26])[C:6]1[CH:11]=[CH:10][C:9]([C:12]([NH:14][CH2:15][C:16]2[CH:24]=[CH:23][CH:22]=[C:21]3[C:17]=2[CH:18]=[CH:19][NH:20]3)=[O:13])=[CH:8][C:7]=1[Cl:25].C1C=NC2N(O)N=NC=2C=1.C(N=C=NC(C)C)(C)C.[S:49]1[CH:53]=[CH:52][CH:51]=[C:50]1[C:54](O)=[O:55]>CN1CCCC1=O>[S:49]1[CH:53]=[CH:52][CH:51]=[C:50]1[C:54]([NH:1][CH2:2][C@@H:3]([C:27]([OH:29])=[O:28])[NH:4][C:5](=[O:26])[C:6]1[CH:11]=[CH:10][C:9]([C:12]([NH:14][CH2:15][C:16]2[CH:24]=[CH:23][CH:22]=[C:21]3[C:17]=2[CH2:18][CH2:19][NH:20]3)=[O:13])=[CH:8][C:7]=1[Cl:25])=[O:55]

Participants

6

Reactant 4

HCID 107002-Thiophenecarboxylic acidHCID 12734DiisopropylcarbodiimideHCID 181649HOAtHCID 688197963-amino-N-[2-chloro-4-[[(1H-indol-4-ylmethyl)amino]carbonyl]benzoyl]-L-alanine

Product 1

HCID 60115142N-[2-chloro-4-[[(2,3-dihydro-1H-indol-4-ylmethyl)amino]carbonyl]benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To 3-amino-N-[2-chloro-4-[[(1H-indol-4-ylmethyl)amino]carbonyl]benzoyl]-L-alanine on Wang resin (Example 69; 100 mg) was added a solution of HOAT (70 mg, 0.51 mmol), diisopropylcarbodiimide (80 μL, 0.51 mmol), and thiophene-2-carboxylic acid (70 mg, 0.55 mmol) in 1-methyl-2-pyrrolidinone (1 mL). The mixture was agitated for 2 h and then the resin was filtered and washed extensively with dichloromethane and methanol. Cleavage of the product was effected with triethylsilane/trifluoroacetic acid/dichloromethane (2:1:1; 1 mL) at room temperature for 30 min. The solvent was evaporated and the residue was purified by HPLC to give 3-(thiophene-2-carbonyl)amino-N-[2-chloro-4-[[(2,3-dihydro-1H-indol-4-ylmethyl)amino]carbonyl]benzoyl]-L-alanine (10.7 mg).

Workup

  1. filtrationthe resin was filtered
  2. washwashed extensively with dichloromethane and methanol
  3. waitCleavage of the product was effected with triethylsilane/trifluoroacetic acid/dichloromethane (2:1:1; 1 mL) at room temperature for 30 min
  4. customThe solvent was evaporated
  5. customthe residue was purified by HPLC

Sources & evidence

ORD record
ord-9afdeb6dc0174ef1a63b4d0bbb9b560c
Source dataset
uspto-grants-2004_10
Patent number
US06803384B2

Reaction notes

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