2,4,6-Trimethylpyridine → 4-(S)-[2-(S)-Allyloxycarbonylamino-3-(4-carbamimidoyl-phenyl)-propionylamino]-4-(2-carbamoyl-1-(S)-(2-phenylethylcarbamoyl)-ethylcarbamoyl)-butyric acid hydrochloride

HRID 1595143Notes

Reaction equation

HRID 1595143 reaction equation
C([O:5][C:6](=[O:34])[CH2:7][CH2:8][C@H:9]([NH:13][C:14](=[O:33])[C@@H:15]([NH:26][C:27]([O:29][CH2:30][CH:31]=[CH2:32])=[O:28])[CH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:23](=[NH:25])[NH2:24])=[CH:19][CH:18]=1)[C:10]([OH:12])=O)(C)(C)C.[ClH:35].[NH2:36][C@@H:37]([CH2:49][C:50]([NH2:52])=[O:51])[C:38]([NH:40][CH2:41][CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)=[O:39].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.N1C(C)=CC(C)=CC=1C>CN(C=O)C>[ClH:35].[CH2:30]([O:29][C:27]([NH:26][C@@H:15]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:23](=[NH:25])[NH2:24])=[CH:19][CH:18]=1)[C:14]([NH:13][C@H:9]([C:10](=[O:12])[NH:36][C@H:37]([C:38](=[O:39])[NH:40][CH2:41][CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[CH2:49][C:50](=[O:51])[NH2:52])[CH2:8][CH2:7][C:6]([OH:5])=[O:34])=[O:33])=[O:28])[CH:31]=[CH2:32]

Participants

6

Reactant 4

HCID 79532,4,6-TrimethylpyridineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 114429402-(S)-[2-(S)-Allyloxycarbonylamino-3-(4-carbamimidoyl-phenyl)-propionylamino]-pentanedioic acid 5-tert-butyl esterHCID 206836142-(S)-amino-N1-phenylethyl-succinamide hydrochloride

Product 1

HCID 686149964-(S)-[2-(S)-Allyloxycarbonylamino-3-(4-carbamimidoyl-phenyl)-propionylamino]-4-(2-carbamoyl-1-(S)-(2-phenylethylcarbamoyl)-ethylcarbamoyl)-butyric acid hydrochloride

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 2-(S)-[2-(S)-allyloxycarbonylamino-3-(4-carbamimidoyl-phenyl)-propionylamino]-pentanedioic acid 5-tert-butyl ester (48 mg, 0.1 mmol) and 2-(S)-amino-N1-phenylethyl-succinamide hydrochloride (27 mg, 0.1 mmol) in 5 ml of DMF were added at 0° C. HATU (39 mg, 0.1 mmol) and collidine (24.2 mg, 0.2 mmol). The mixture was stirred for 1 hour and then allowed to warm to room temperature. After evaporation the residue was purified by chromatography on Sephadex LH20 employing n-butanol/glacial acetic acid/water (17/1/2) as eluent. Pure fractions were combined. The solvent was evaporated, the residue was taken up in water and the aqueous solution was freeze-dried. Yield: 45 mg (66%). MS: m/z=638.4 (M+H)+.

Workup

  1. customAfter evaporation the residue
  2. customwas purified by chromatography on Sephadex
  3. customThe solvent was evaporated
  4. customthe aqueous solution was freeze-dried

Sources & evidence

ORD record
ord-415ed629b8174bcb828b07ad3073e074
Source dataset
uspto-grants-2001_09
Patent number
US06287794B1

Reaction notes

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