1-Hydroxybenzotriazole → N-[2,6-dichloro-4-[[[(1R)-1-(1-naphthalenyl) ethyl]amino]carbonyl]benzoyl]-3-[(thiophene-2-carbonyl)amino]-L-alanine, methyl ester

HRID 1352094Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1352094
[Cl:1][C:2]1[CH:10]=[C:9]([C:11]([NH:13][C@@H:14]([C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:19]=[CH:18][CH:17]=2)[CH3:15])=[O:12])[CH:8]=[C:7]([Cl:26])[C:3]=1[C:4](O)=[O:5].Cl.[CH3:28][O:29][C:30](=[O:42])[C@H:31]([CH2:33][NH:34][C:35]([C:37]1[S:38][CH:39]=[CH:40][CH:41]=1)=[O:36])[NH2:32].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C>CN(C)C=O>[Cl:1][C:2]1[CH:10]=[C:9]([C:11]([NH:13][C@@H:14]([C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:19]=[CH:18][CH:17]=2)[CH3:15])=[O:12])[CH:8]=[C:7]([Cl:26])[C:3]=1[C:4]([NH:32][C@H:31]([C:30]([O:29][CH3:28])=[O:42])[CH2:33][NH:34][C:35]([C:37]1[S:38][CH:39]=[CH:40][CH:41]=1)=[O:36])=[O:5]

Komponenten

7

Edukt 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 599772642,6-dichloro-4-[[[(1R)-1-(1-naphthalenyl)ethyl]amino]carbonyl]benzoic acidHCID 688207093-(thiophene-2-carbonyl)amino-L-alanine methyl ester hydrochloride

Produkt 1

HCID 131723047N-[2,6-dichloro-4-[[[(1R)-1-(1-naphthalenyl) ethyl]amino]carbonyl]benzoyl]-3-[(thiophene-2-carbonyl)amino]-L-alanine, methyl esterAusbeute 17 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A solution of 2,6-dichloro-4-[[[(1R)-1-(1-naphthalenyl)ethyl]amino]carbonyl]benzoic acid (Example 38; 1.00 g, 2.6 mmol), 3-(thiophene-2-carbonyl)amino-L-alanine, methyl ester hydrochloride (Example 301; 680 mg, 2.6 mmol), HBTU (1.27 g, 3.35 mmol), HOBT (450 mg, 3.3 mmol), and diisopropylethylamine (1.33 g, 10.3 mmol) in N,N-dimethylformamide (20 mL) was stirred at room temperature over the weekend. The solvent was evaporated and ethyl acetate (200 mL) was added. The solution was washed with 1 M HCl (100 mL), saturated aqueous sodium hydrogen carbonate (Note: some material was lost due to effervescence at this stage) and brine (200 mL each), then dried (MgSO4), filtered, evaporated and chromatographed (70% ethyl acetate/hexanes) to give N-[2,6-dichloro-4-[[[(1R)-1-(1-naphthalenyl)ethyl]amino]carbonyl]benzoyl]-3-[(thiophene-2-carbonyl)amino]-L-alanine, methyl ester (260 mg, 17%) as a white solid.

Aufarbeitung

  1. customThe solvent was evaporated
  2. additionethyl acetate (200 mL) was added
  3. washThe solution was washed with 1 M HCl (100 mL), saturated aqueous sodium hydrogen carbonate (
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. customchromatographed (70% ethyl acetate/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-9b43ccfdfe1b4df68d20c95ef1a5b85f
Quelldatensatz
uspto-grants-2007_05
Patentnummer
US07217728B2

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